TY  - JOUR
A1  - Gessler, Manfred
A1  - Thomas, G. H.
A1  - Couillin, P.
A1  - Junien, C.
A1  - McGillivray, B. C.
A1  - Hayden, M.
A1  - Jaschek, G.
A1  - Bruns, G. A.
T1  - A deletion map of the WAGR region on chromosome II
N2  - The WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) region has been assigned to chromosome 11p13 on the basis of overlapping constitutional deletions found in affected individuals. We have utilized 31 DNA probes which map to the WAGR deletion region, together with six reference loci and 13 WAGR-related deletions, to subdivide this area into 16 intervals. Specific intervals have been correlated with phenotypic features, leading to the identification of individual subregions for the aniridia and Wilms tumor loci. Delineation, by specific probes, of multiple intervals above and below the critical region and of five intervals within the overlap area provides a framework map for molecular characterization of WAGR gene loci and of deletion boundary regions.
KW  - Biochemie
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59255
ER  - 
TY  - JOUR
A1  - Gessler, Manfred
A1  - Bruns, G. A. P.
T1  - A physical map around the WAGR complex on the short arm of chromosome 11
N2  - A long-range restriction map of part of the short arm of ehromosome 11 including the WAGR region has been constructed using pulsed-field gel electrophoresis and a number of infrequently cutting restriction enzymes. A total of 15.4 Mbp has been mapped in detall, extending from proximal 11p14 to the distal part of 11p12. The map localizes 35 different DNA probes and reveals at least nine areas with features eharaeteristle of BTF islands, some of which may be candidates for the different loci underlying the phenotype of the WAGR syndrome. This map will furthermore allow screening of DNA from individuals with WAGR-related phenotypes and from Wilms tumors for associated chromosomal rearrangements.
KW  - Biochemie
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59246
ER  - 
TY  - JOUR
A1  - Vortkamp, A.
A1  - Thias, U.
A1  - Gessler, Manfred
A1  - Rosenkranz, W.
A1  - Kroisel, P. M.
A1  - Tommerup, N.
A1  - Kruger, G.
A1  - Gotz, J.
A1  - Pelz, L.
A1  - Grzeschik, Karl-Heinz
T1  - A somatic cell hybrid panel and DNA probes for physical mapping of human chromosome 7p
N2  - No abstract available
KW  - Biochemie
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59217
ER  - 
TY  - JOUR
A1  - Schwartz, Faina
A1  - Neve, Rachel
A1  - Eisenman, Robert
A1  - Gessler, Manfred
A1  - Bruns, Gail
T1  - A WAGR region gene between PAX-6 and FSHB expressed in fetal brain
N2  - Developmental delay or mental retardation is a frequent component of multi-system anomaly syndromes associated with chromosomal deletions. Isolation of genes involved in the mental dysfunction in these disorders should define loci important in brain formation or function. We have identified a highly conserved locus in the distal part of 11 p 13 that is prominently expressed in fetal brain. Minimal expression is observed in a number of other fetal tissues. The gene maps distal to PAX-6 but proximal to the loci for brain-derived neurotrophic factor (BDNF) and the beta subunit of follicle stimulating hormone (FSHB), within a region previously implicated in the mental retardation component of some WAGR syndrome patients. Within fetal brain, the corresponding transcript is prominent in frontal, motor and primary visual cortex as weil as in the caudate-putamen. The characteristics of this gene, including the striking evolutionary conservation at the locus, suggest that the encoded protein may function in brain development.
KW  - Biochemie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59125
ER  - 
TY  - JOUR
A1  - Barnekow, Angelika
A1  - Gessler, Manfred
T1  - Activation of the pp60\(^{c-src}\) kinase during differentiation of monomyelocytic cells in vitro
N2  - Tbe proto-oncogene c-src, the cellular homolog of the Rous sarcoma virus (RSV) transforming gene v-src, is expressed in a tissue-specific and age-dependent manner. Its physiological function, although still unknown, appears to be more closely related to differentiation processes than to proliferation processes. To obtain more information about the physiological role of the c-src gene in cells, we have studied differentiation-dependent alterations using the human HL-60 leukaemia cell line as a model system. Induction of monocytic and granulocytic differentiation of HL-60 cells by 12-0-tetradecanoylphorbol-13-acetate (TPA) and dimethylsulfoxide (DMSO) is associated with an activation of the pp60<sup>c-src</sup> tyrosine kinase, but not with increased c-src gene expression. Control experiments exclude an interaction of TPA and DMSO themselves with the pp60<sup>c-src</sup> kinase.
KW  - Biochemie
KW  - c-src
KW  - differentiation
KW  - protein tyrosine kinase
KW  - protooncogene
Y1  - 1986
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59278
ER  - 
TY  - JOUR
A1  - Velours, J.
A1  - Esparza, M.
A1  - Hoppe, J.
A1  - Sebald, Walter
A1  - Guerin, B.
T1  - Amino acid sequence of a new mitochondrially synthesized proteolipid of the ATP synthase of Saccharomyces cerevisiae
N2  - The purification and the amino acid sequence of a proteolipid translated on ribosomes in yeast mitochondria is reported. This protein, which is a subunit of the A TP synthase, was purified by extraction with chloroform/methanol (2/1) and subsequent chromatography on phosphocellulose and reverse phase h.p.l.c. A mol. wt. of 5500 was estimated by chromatography on Bio-Gel P-30 in 8011/o fonnie acid. The complete amino acid sequence of this protein was determined by automated solid phase Edman degradation of the whole protein and of fragments obtained after cleavage with cyanogen bromide. The sequence analysis indicates a length of 48 amino acid residues. The calculated mol. wt. of 5870 corresponds to the value found by gel chromatography. This polypeptide contains three basic residues and no negatively charged side chain. The three basic residues are clustered at the C terminus. The primary structure of this protein is in full agreement with the predicted amino acid sequence of the putative polypeptide encoded by the mitochondrial aap1 gene recently discovered in Saccharomyces cerevisiae. Moreover, this protein shows 5011/o homology with the amino acid sequence of a putative polypeptide encoded by an unidentified reading frame also discovered near the mitochondrial ATPase subunit 6 genein Aspergillus nidulans.
KW  - Biochemie
KW  - ATP synthase
KW  - mitochondrially translated
KW  - proteolipid
KW  - sequence subunit
Y1  - 1984
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62695
ER  - 
TY  - JOUR
A1  - Hoppe, J.
A1  - Sebald, Walter
T1  - Amino acid sequence of the proteolipid subunit of the proton-translocating ATPase complex from the thermophilic bacterium PS-3
N2  - No abstract available
KW  - Biochemie
Y1  - 1980
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62754
ER  - 
TY  - JOUR
A1  - Müller, T.
A1  - Sebald, Walter
A1  - Oschkinat, H.
T1  - Antagonist design through forced electrostatic mismatch
N2  - No abstract available
KW  - Biochemie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62408
ER  - 
TY  - JOUR
A1  - Müller, T.
A1  - Dieckmann, T.
A1  - Sebald, Walter
A1  - Oschkinat, H.
T1  - Aspects of receptor binding and signalling of interleukin-4 investigated by site-directed mutagenesis and NMR spectroscopy
N2  - Cytokines are hormones that carry information from ceJI to ceH. This information is read from their surface upon binding to transmembrane receptors and by the subsequent initiation of receptor oligomerization. An inftuence on this process through mutagenesis on the hormone surface is highly desirab)e for medical reasons. However, an understanding of hormone-receptor interactions requires insight into the structural changes introduced by the mutations. In this line structural studies on human TL-4 and the medically important IL-4 antagonists YI24D and Y124G are presented. The site a.round YI24 is an important epitope responsible for the a.bility of 11-4 t.o ca.use a signal in the target cells. It is shown that the local main-chain structure around residue 124 in the variants remains unchanged. A strategy is presented here which allows the study of these types of proteins and their variants by NMR which does not require carbon Iabeiied sa.mples.
KW  - Biochemie
KW  - Interleukin-4
KW  - protein structure
KW  - NMR
KW  - signal transduction
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62444
ER  - 
TY  - JOUR
A1  - von Jagow, Gerhard
A1  - Sebald, Walter
T1  - b-Type cytochromes
N2  - No abstract available
KW  - Biochemie
Y1  - 1980
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-47383
ER  - 
TY  - JOUR
A1  - Sebald, Walter
T1  - Biogenesis of mitochondrial ATPase
N2  - No abstract available
KW  - Biochemie
Y1  - 1977
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-47362
ER  - 
TY  - JOUR
A1  - Sebald, Walter
A1  - Werner, S
A1  - Weiss, H
T1  - Biogenesis of mitochondrial membrane proteins in Neurospora crassa
N2  - no abstract available
KW  - Biochemie
KW  - Neurospora crassa
Y1  - 1979
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-82055
ER  - 
TY  - JOUR
A1  - Gabellini, N.
A1  - Harnisch, U.
A1  - McCarthy, J. E.
A1  - Hauska, G.
A1  - Sebald, Walter
T1  - Cloning and expression of the fbc operon encoding the FeS protein, cytochrome b and cytochrome c\(_1\) from the Rhodopseudomonas sphaeroides b/c\(_1\) complex
N2  - The gene for the FeS protein of the Rhodopseudomonas sphaeroides b/c1 complex was identified by means of crosshybridization with a segment of the gene encoding the corresponding FeS protein of Neurospora crassa. Plasmids (pRSF1-14) containing the cross-hybridizing region, covering in total 13.5 kb of chromosomal DNA, were expressed in vitro in a homologous system. One RSF plasmid directed the synthesis of all three main polypeptides of the R. sphaeroides blc1 complex: the FeS protein, cytochrome b and cytochrome c1• The FeS protein and cytochrome c1 were apparently synthesized as precursor fonns. None of the pRSF plasmids directed the synthesis of the 10-kd polypeptide found in b/c1 complex preparations. Partial sequencing of the cloned region was performed. Several sites of strong homology between R. sphaeroides and eukaryotic polypeptides of the b/c1 complex were identified. The genes encode the three b/c1 polypeptides in the order: (5') FeS protein, cytochrome b, cytochrome c1• The three genes are transcribed to give a polycistronic mRNA of 2.9 kb. This transcriptional unit has been designated the jbc operon; its coding capacity corresponds to the size of the polycistronic mRNA assuming that only the genes for the FeS protein (jbcF), cytochrome b (jbcß) and cytochrome c1 (jbcC) are present. This could indicate that these three subunits constitute the minimal catalytic unit of the b/c1 complex from photosynthetic membranes.
KW  - Biochemie
KW  - R. sphaeroidesl
KW  - b/c1 complex
KW  - gene
KW  - cloning
KW  - in vitro expression
KW  - polycistronic mRNA
Y1  - 1985
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62642
ER  - 
TY  - JOUR
A1  - Schwarz, Klaus
A1  - Hameister, Horst
A1  - Gessler, Manfred
A1  - Grzeschik, Karl-Heinz
A1  - Hansen-Hagge, Thomas E.
A1  - Bartram, Claus R.
T1  - Confirmation of the localization of the human recombination activating gene 1 (RAG1) to chromosome 11p13
N2  - The human recombination activating gene 1 (RAGl) has previously been mapped to chromosomes 14q and 11 p. Here we confirm the chromosome 11 assignment by two independent approaches: autoradiographic and fluorescence in situ hybridization to metaphase spreads and analysis of human-hamster somatic cell hybrid DNA by the polymerase chain reaction (PCR) and Southern blotting. Our results unequivocally localize RAG1 to llp13.
KW  - Biochemie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59136
ER  - 
TY  - JOUR
A1  - Weiss, H.
A1  - Sebald, Walter
A1  - Schwab, A. J.
A1  - Kleinow, W.
A1  - Lorenz, B.
T1  - Contribution of mitochondrial and cytoplasmic protein synthesis to the formation of cytochrome b and cytochrome aa\(_3\)
N2  - A cytochrome b preparation from Neurospora crassa mitochondria is found to consist of three polypeptides (apparent molecular weight 10 000, 11 000 and 32 000), a cytochrome aa3 preparation of six to seven polypeptides (apparent molecular weight 8 000, 11 000, 13 000, 18 000, 28 000 and 36 000). Selective incorporation of radioactive amino acids by eilher mitochondrial protein synthesis when the cytoplasmic one is blocked or by the cytoplasmic protein synthesis, when the mitochondrial one is blocked, indicates that one cytochrome b polypeptide (mw 32 000) and one to three cytochrome aa3 polypeptides (mw 36 000, 28 000 and 18 000) are mitochondrial translation products, the other cytochrome b and cytochrome aa3 polypeptides cytoplasmic translation products. The delayed appearance of labeling in the cytochrome b and cytochrome aa3 polypeptides compared to the average cell protein after a pulse of <~H leueine revealed that these polypeptides are derived from separate pools of precursor polypeptides. The pool sizes range from 2 p. cent to 25 p. cent of the amount of the corresponding polypeptide present in the cytochromes. The 32 000 molecular weight polypeptide of cytochrome band at least the 18 000 molecular weight polypeptide of cytochrome aa\(_3\) are mitochondrial translation products as well in the fungus Neurospora crassa as in the insect Locusta migratoria. So, despite the fact that the size of mitochondrial DNA and mitochondrial ribosomes is reduced in insects, the products have maintained their characteristics.
KW  - Biochemie
Y1  - 1973
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62835
ER  - 
TY  - JOUR
A1  - Kruse, N.
A1  - Tony, H. P.
A1  - Sebald, Walter
T1  - Conversion of human interleukin-4 into a high affinity antagonist by a single amino acid replacement
N2  - lnterleukin-4 (IL-4) represents a prototypic lymphokine (for a recent review see Paul, 1991). It promotes differentiation of B-cells and the proliferation of T- and B-cell, and other cell types of the lymphoid system. An antagonist of human IL-4 was discovered during the studies presented here after Tyr124 of the recombinant proteinbad been substituted by an aspartic acid residue. This IL-4 variant, Y124D, bound with high affinity to the IL-4 receptor (K\(_D\) = 310 pM), but retained no detectable proliferative activity for T -<:ells and inhibited IL-4-dependent T -cell proliferation competitively (K\(_i\) = 620 pM). The loss of efficacy in variant Y124D was estimated to be > 100-fold on the basis of a weak partial agonist activity for the very sensitive induction of CD23 positive B-cells. The subsitution of Tyr124 by either phenylalanine, histidine, asparagine, Iysine or glycine resulted in partial agonist variants with unaltered receptor binding atTmity and relatively small deficiencies in efficacy. These results demoostrate that high affinity binding and signal generation can be uncoupled efticiently in a Iigand of a receptor betonging to the recently identified hematopoietin receptor family. In addition we show for the first time, that a powerful antagonist acting on the IL-4 receptor system can be derived from the IL-4 protein.
KW  - Biochemie
KW  - drug design
KW  - partial agonists
KW  - receptor signalling
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62469
ER  - 
TY  - JOUR
A1  - Sebald, Walter
A1  - Schwab, A. J.
A1  - Bücher, T.
T1  - Cycloheximide resistant amino acid incorporation into mitochondrial protein from Neurospora crassa in vivo
N2  - No abstract available
KW  - Biochemie
Y1  - 1969
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62900
ER  - 
TY  - JOUR
A1  - Weiss, H.
A1  - Sebald, Walter
A1  - Bücher, T.
T1  - Cycloheximide resistant incorporation of amino acids into a polypeptide of the cytochrome oxidase of Neurospora crassa
N2  - Radioaetive leueine was ineorporated by N eurospora crassa mitoehondria in vivo in the presence of cyeloheximide. When the membrane protein of these mitochondria was ehromatographieally separated on oleyl polymethaerylie aeid resin, & nurober of fraetions were obtained whieh differ with respeet to their eontents of radioaetivity and eytoehromes. The highest speeifie radioaetivity was found in the fraction eontaining eytoehrome aa3• This fraetion proved to be a pure and enzymatically aetive cytoehrome oxidase. Its ratio of absorbanee at 280 nm (ox)/ 443 nm (red.) was 2.1. By means of sodium dodeeylsulfate gel-electrophoresis, this enzymewas separated into five polypeptides with molecular weights of 30000, 20000, 13000, 10000, and 8000. Only the polypeptide with the molecular weight 20000 displayed a high specific radioaetivity.
KW  - Biochemie
Y1  - 1971
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62866
ER  - 
TY  - JOUR
A1  - Merz, H.
A1  - Fliedner, A.
A1  - Lehrnbecher, T.
A1  - Sebald, Walter
A1  - Müller-Hermelink, H. K.
A1  - Feller, A. C.
T1  - Cytokine expression in B-cell non-Hodgkin lymphomas
N2  - No abstract available
KW  - Biochemie
Y1  - 1990
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62539
ER  - 
TY  - JOUR
A1  - Merz, H.
A1  - Fliedner, A.
A1  - Orscheschek, K.
A1  - Binder, T.
A1  - Sebald, Walter
A1  - Müller-Hermelink, H. K.
A1  - Feller, A. C.
T1  - Cytokine expression in T-cell lymphomas and Hodgkin's disease. Its possible implication in autocrine or paracrine production as a potential basis for neoplastic growth
N2  - No abstract available
KW  - Biochemie
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62483
ER  - 
TY  - JOUR
A1  - Tony, H. P.
A1  - Shen, B. J.
A1  - Reusch, P.
A1  - Sebald, Walter
T1  - Design of human interleukin-4 antagonists inhibiting interleukin-4-dependent and interleukin-13-dependent responses in T-cells and B-cells with high efficiency
N2  - Human interleukin-4 possesses two distinct sites for receptor activation. A signaHing site, comprising residues near the C-terminus on helix D, determines the efficacy of interleukin-4 signal transduction without affecting the binding to the interleukin-4 receptor a subunit. A complete antagonist and a series of low-efficacy agonist variants of human interleukin-4 could be generated by introducing combinations of two or three negatively charged aspartic acid residues in this site at positions 121, 124, and 125. One of the double variants, designated [R121D,Y124D]interleukin-4, with replacements of böth Arg121 and Tyr124 by aspartic acid residues was completely inactive in all analysed cellular responses. The loss of efficacy in [R121D,Y124D]interleukin-4 is estimated to be larger than 2000-fold. Variant [R121D,Y124D]interleukin-4 was also a perfect antagonist for inhibition of interleukin-13-dependent responses in B-cells and the TF-1 cellline with a K\(_i\) value of approximately 100 pM. In addition, inhibition of both interleukin-4-induced and interleuk.in-13- induced responses could be obtained by monoclonal antibody X2/45 raised against interleukin-4Rm the extracellular domain of the interleuk.in-4 receptor a subunit. These results indicate that efficient interleukin-4 antagonists can be designed on the basis of a sequential two-step activation model. In addition, the experiments indicate the functional participation of the interleukin-4 receptor a subunit in the interleukin-13 receptor system.
KW  - Biochemie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62394
ER  - 
TY  - JOUR
A1  - Schwab, A. J.
A1  - Sebald, Walter
A1  - Weiss, H.
T1  - Different pool sizes of the precursor polypeptides of cytochrome oxidase from Neurospora crassa.
N2  - Pulse-labelling experiments with growing Neurospora crassa revealed that the polypeptides composing the protein moiety of a cytochrome oxidase preparation are derived from at least four independent pools of precursor polypeptides. The pool sizes range from 2 ° f 0 to 25 °/0 of the amount of the corresponding polypeptide present in cytochrome oxidase. The smallest pool is assigned to a polypeptide of mitochondrial origm. Serial pools were found for one of the polypeptides.
KW  - Biochemie
Y1  - 1972
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62841
ER  - 
TY  - JOUR
A1  - Gessler, Manfred
A1  - Barnekow, Angelika
T1  - Differential expression of the cellular oncogenes c-src and c-yes in embryonal and adult chicken tissues
N2  - The cellular onc-genes c-src and c-yes are expressed very differently during chicken embryonic development. The c-src mRNA and its translational product are detectable at high levels in brain extracts of chicken embryos and adult chickens, whereas muscle extracts show an age-dependent decrease in the amounts of c-src-specific mRNA and pp60<sup>c-src</sup> kinase activity. In contrast, the Ievels of c-yes mRNA in brain, heart, and muscle are relatively low in early embryonic stages and increase later on to values comparable to those found for liver, while in adult animals the pattern of c-yes expression is similar to that of the c-src gene. From the close correlation between the Ievels of pp60<sup>c-src</sup>, its enzymatic activity, and its corresponding mRNA at a given stage of development and in given tissues, it appears that the expression of pp60<sup>c-src</sup> is primarily controlled at the level of transcription. It is suggested that because of the different patterns of expression, the two cellular oncogenes, c-src and c-yes, play different roles in cell proliferation during early embryonic stages as weil as in ensuing differentiation processes.
KW  - Biochemie
Y1  - 1984
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59289
ER  - 
TY  - JOUR
A1  - Poulat, F.
A1  - Morin, D.
A1  - Konig, A.
A1  - Brun, P.
A1  - Giltay, J.
A1  - Sultan, C.
A1  - Dumas, R.
A1  - Gessler, Manfred
A1  - Berta, P.
T1  - Distinct molecular origins for Denys-Drash and Frasier syndromes
N2  - The direct involvment of the Wilm's tumor suppressor gene (WTl) in Denys-Drash syndrome through mutations within exons 8 or 9 has recently been established. The absence of such alterations in three patients with Frasier syndrome provides a molecular basis for distinguishing these two syndromes that are associated with streak gonads, pseudohermaphroditism and renal failure.
KW  - Biochemie
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59172
ER  - 
TY  - JOUR
A1  - Sebald, Walter
A1  - Bücher, T.
A1  - Olbrich, B.
A1  - Kaudewitz, F.
T1  - Electrophoretic pattern of and amino acid incorporation in vitro into the insoluble mitochondrial protein of neurospora crassa wild type and mi-1 mutant
N2  - No abstract available
KW  - Biochemie
Y1  - 1968
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62926
ER  - 
TY  - JOUR
A1  - McCarthy, J. E.
A1  - Sebald, Walter
A1  - Gross, G.
A1  - Lammers, R.
T1  - Enhancement of translational efficiency by the Escherichia coli atpE translational initiation region: its fusion with two human genes
N2  - No abstract available
KW  - Biochemie
Y1  - 1986
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62626
ER  - 
TY  - JOUR
A1  - Konig, Anja
A1  - Jakubiczka, Sybille
A1  - Wieacker, Peter
A1  - Schlösser, Hans W.
A1  - Gessler, Manfred
T1  - Further evidence that imbalance of WT1 isoforms may be involved in Denys-Drash syndrome
N2  - No abstract available
KW  - Biochemie
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59167
ER  - 
TY  - JOUR
A1  - Gessler, Manfred
A1  - Konig, Anja
A1  - Moore, Jay
A1  - Qualman, Steven
A1  - Arden, Karen
A1  - Cavenee, Webster
A1  - Bruns, Gail
T1  - Homozygous inactivation of WTI in a Wilms' tumor associated with the WAGR syndrome
N2  - Wilms' tumor is a childhood nephroblastoma that is postulated to arise through the inactivation of a tumor suppressor gene by a two-hit mechanism. A candidate II p 13 Wilms' tumor gene, WTI, has been cloned and shown to encode a zinc finger protein. Patients with the WAGR syndrome (Wilms' tumor, aniridia, genitourinary abnormalities, and mental retardation) have a high risk of developing Wilms' tumor and they carry constitutional deletions of one chromosome II allele encompassing the WTI gene. Analysis of the remaining WTI allele in a Wilms' tumor from a WAGR patient revealed the deletion of a single nucleotide in exon 7. This mutation likely played a key role in tumor formation, as it prevents translation of the DNA-binding zinc finger domain that is essential for the function of the WTI polypeptide as a transcriptional regulator.
KW  - Biochemie
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59146
ER  - 
TY  - JOUR
A1  - Wolf, Markus
A1  - Klug, Jörg
A1  - Hackenberg, Reinhard
A1  - Gessler, Manfred
A1  - Grzeschik, Karl-Heinz
A1  - Beato, Miguel
A1  - Suske, Guntram
T1  - Human CC10, the homologue of rabbit uteroglobin: genomic cloning, chromosomal localization and expression in endometrial cell lines
N2  - No abstract available
KW  - Biochemie
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59206
ER  - 
TY  - JOUR
A1  - Sebald, Walter
A1  - Wachter, E.
A1  - Tzagoloff, A.
T1  - Identification of amino acid substitutions in the dicyclohexylcarbodiimide-binding subunit of the mitochondrial ATPase complex from oligomycin-resistant mutants of Saccharomyces cerevisiae
N2  - No abstract available
KW  - Biochemie
Y1  - 1979
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62770
ER  - 
TY  - JOUR
A1  - Hoppe, J.
A1  - Schairer, HU
A1  - Sebald, Walter
T1  - Identification of amino-acid substitutions in the proteolipid subunit of the ATP synthase from dicyclohexylcarbodiimide-resistant mutants of Escherichia coli
N2  - The amino acid sequence of the proteolipid subunit of the A TP synthase was analyzed in six mutant strains from Escherichia coli K 12, selected for their increased resistance towards the inhibitor N,N'-dicyclohexylcarbodiimide. All six inhibitor-resistant mutants were found to be altered at the same position of the proteolipid, namely at the isoleucine at residue 28. Two substitutions could be identified. In type I this residue was substituted by a valine resulting in a moderate decrease in sensitivity to dicyclohexylcarbodiimide. Type II contained a threonine residue at this position. Here a strong resistance was observed. These two amino acid substitutions did not influence functional properties of the ATPase complex. ATPase as well as A TP-dependent proton-translocating activities of mutant membranes were indistinguishable from the wild type. At elevated concentrations, dicyclohexylcarbodiimide still bound specifically to the aspartic acid at residue 61 of the mutant proteolipid as in the wild type, and thereby inhibited the activity of the ATPase complex. It is suggested that the residue 28 substituted in the resistant mutants interacts with dicyclohexylcarbodiimide during the reactions leading to the covalent attachment of the inhibitor to the aspartic acid at residue 61. This could indicate that these two residues are in close vicinity and would thus provide a first hint on the functional conformation of the proteolipid. Its polypeptide chain would have to fold back to bring together these two residues separated by a segment of 32 residues.
KW  - Biochemie
Y1  - 1980
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-47374
ER  - 
TY  - JOUR
A1  - Jackl, G.
A1  - Sebald, Walter
T1  - Identification of two products of mitochondrial protein synthesis associated with mitochondrial adenosine triphosphatase from Neurospora crassa
N2  - Soluble mitochondrial ATPase (F1) isolated from Neurospora crassa is resolved by dodecylsulfate- gel electrophoresis into five polypeptide bands with apparent molecular weights of 59000, 55000, 36000, 15000 and 12000. At least nine further polypeptides remain associated with ATPase after disintegration of mitochondria with Triton X-100 as shown by the analysis of an immunoprecipitate obtained with antiserum to F 1 A TPase. Two of the associated polypeptides with apparent molecular weights of 19000 and 11000 are translated on mitochondrial ribosomes, as demonstrated by incorporation in vivo of radioactive leueine in the presence of specific inhibitors of mitochondrial (chloramphenicol) and extramitochondrial ( cycloheximide) protein synthesis. The appearance of mitochondrial translation products in the immunoprecipitated A TPase complex is inhibited by' cycloheximide. The same applies for some of the extramitochondrial translation products in the presence of chloramphenicol. This suggests that both types of polypeptides are necessary for the assembly of the A TPase complex.
KW  - Biochemie
Y1  - 1975
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62812
ER  - 
TY  - JOUR
A1  - Kübler, N.
A1  - Reuther, J.
A1  - Kirchner, T.
A1  - Pfaff, M.
A1  - Müller-Hermelink, H. K.
A1  - Albert, R.
A1  - Sebald, Walter
T1  - IgG monoclonal antibodies that inhibit osteoinductivity of human bone matrix-derived proteins (hBMP/NCP)
N2  - Monoclonal hBMP/NCP (human bone morphogenetic protein anrl associaterl noncollagenous proteins) antiborlies of the lgG class were prorlucerl. In vitro, 12 of 19 hBMP/NCP antiborlies showerl functional inhibition of hBMP/ NCP-induced chondroneogenesis in a neonatal muscle tissue assay. Inducing factors were characterized by their inhibiting antibodies with immunoblotting. Several peptide factors seem to be involved in the cascade of inducerl chondro- and osteogenesis.
KW  - Biochemie
KW  - bone morphogenetic proteins
KW  - neutralizing antibodies
KW  - cartilage induction
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62388
ER  - 
TY  - JOUR
A1  - Werner, S.
A1  - Sebald, Werner
T1  - Immunological techniques for studies on the biogenesis of mitochondrial membrane proteins
N2  - no abstract available
KW  - Biochemie
Y1  - 1981
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-82044
ER  - 
TY  - JOUR
A1  - Neupert, W.
A1  - Sebald, Walter
A1  - Schwab, A. J.
A1  - Massinger, P.
A1  - Bücher, T.
T1  - Incorporation in vivo of \(^{14}\)C-labelled amino acids into the proteins of mitochondrial ribosomes from Neurospora crassa sensitive to cycloheximide and insensitive to Chloramphenicol
N2  - Radioactive amino acids were incorporated in vivo into N eurospora crassa cells, and the mitochondrial ribosomes were isolated. The incorporation of radioactivity into the proteins of these ribosomes was inhibited by cycloheximide, but not by chloramphenicol. It is therefore concluded that these proteins are synthesized on the cycloheximide sensitive and chloramphenicol insensitive cytoplasmic ribosomes.
KW  - Biochemie
Y1  - 1969
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62884
ER  - 
TY  - JOUR
A1  - Sebald, Walter
A1  - Hofstötter, T.
A1  - Hacker, D.
A1  - Bücher, T.
T1  - Incorporation of amino acids into mitochondrial protein of the flight muscle of Locusta migratoria in vitro and in vivo in the presence of cycloheximide
N2  - No abstract available
KW  - Biochemie
Y1  - 1969
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62919
ER  - 
TY  - JOUR
A1  - Sebald, Walter
A1  - Weiss, H.
A1  - Jackl, G.
T1  - Inhibition of the assembly of cytochrome oxidase in Neurospora crassa by chloramphenicol
N2  - Cytochrome oxidasewas prepared from Neurospora crassa by chromatography on oleyl polymethacrylic acid resin and separated into seven polypeptides by polyacrylamide gel electrophoresis in the presence of sodium dodecylsulfate. Incorporation oflabelled amino acids into the single polypeptideswas investigated after a pulse labelling in the absence and presence of chloramphenicol, and afterwashing out the inhibitor. Chloramphenicol (4 mg/ml) inhibited amino acid incorporation into all polypeptides 90-95%• while labeHing of the whole membrane protein was inhibited only 30%• Mter washing out the inhibitor and further growth of the cells. the four smaller polypeptides were highly labelled, whereas the other polypeptides showed only a. small increase in radioactivity. It is concluded that the four small-sized polypeptides of cytochrome oxidase are synthesized but not integrated into the functional enzyme under the action of chloramphenicol.
KW  - Biochemie
Y1  - 1972
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62852
ER  - 
TY  - JOUR
A1  - Lehrnbecher, T.
A1  - Merz, H.
A1  - Sebald, Walter
A1  - Poot, M.
T1  - Interleukin 4 drives phytohemagglutinin-activated T cells through several cell cycles: no synergism between interleukin 2 and interleukin 4
N2  - Cell kinetic studies of T cells stimulated with the interleukin 2 (11-2), D-4, or both lymphokines were performed with conventional [3H] thymidine incorporation and with the bivariate BrdU/Hoechst technique. 11-2 and 11-4 are able to drive phytohemagglutininactivated T cells through more than one cell cycle. Neither synergistic nor inhibitory efl'ect on T -cell proliferationwas seen for the stimulation with both 11-2 and 11-4 as compared with the effect ofll-2 alone. The quantitative data ofthe cell cycle distribution ofphytohemagglutininactivated T cells suggestthat the population ofll-4-responsive cells is at least an overlapping population, if not a real subset of the ·population of the 11-2-responsive cells.
KW  - Biochemie
KW  - BrdU-Hoechst
KW  - cell cycle
KW  - flow cytometry
KW  - interleukin 2
KW  - interleukin 4
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62491
ER  - 
TY  - JOUR
A1  - Lehrnbecher, T.
A1  - Poot, M.
A1  - Orscheschek, K.
A1  - Sebald, Walter
A1  - Feller, A. C.
A1  - Merz, H.
T1  - Interleukin 7 as interleukin 9 drives phytohemagglutinin-activated T cells through several cell cycles; no synergism between interleukin 7, interleukin 9 and interleukin 4
N2  - The effects of the interlenkins IL-7 and IL-9 on cell cycle progression were investigated by conventional [3H]thymidine incorporation and by the bivariate BrdU/Hoechst technique. 8oth IL· 7 and IL-9 drive phytohemagglutinin-activated T cells through more than one cell cycle, but IL-7 wasmorepotent on cell cycle progression than IL-9. Neither synergistic nor inhibitory effects were seen between various combinations of the lymphokines IL-7, IL-9 and IL-4 compared to each lymphokine alone. When T cells are activated with phytohemagglutinin for 3 days, all or most IL-4 responsive cells respond to IL-7 as weil, whereas only a part of IL-7 responders are IL-4 responders. In contrast, when T cells are activated with phytohemagglutinin for 7 days, the quantitative data of the cell cycle distribution soggest that the population of IL-7 responders is at least an overlapping, if not a real subset of the population of the IL-4 responders.
KW  - Biochemie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62438
ER  - 
TY  - JOUR
A1  - Preiser, J. C.
A1  - Schmartz, D.
A1  - Van der Linden, P.
A1  - Content, J.
A1  - Vanden Bussche, P.
A1  - Buurman, W.
A1  - Sebald, Werner
A1  - Dupont, E.
A1  - Pinsky, M. R.
A1  - Vincent, J. L.
T1  - Interleukin-6 administration has no acute hemodynamic or hematologic effect in the dog
N2  - To investigate the possible hemodynamic efl'ects of interleukin-6 (IL-6), a single dose of 15 mcg/kg of recombinant IL-6 isolated from Escherichia coli was injected intravenously in six pentobarbital-anesthetized dogs. After 30 min, saline infusion was performed to maintain the - pulmonary artery balloon-occluded pressure at baseline Ievel. The animals were observed for up to 5 hours. No other hemodynamic alteration was observed than a gradual decline in cardiac output attributed to anesthesia. Hematologic variables, blood glucose, and total serum proteins were also constant. IL-6 levels were markedly elevated in the blood, bot no tumor necrosis factor activity was detected. Thus a primary role for IL-6 in the early cardiovascular alterations associated with septic shock seems unlikely.
KW  - Biochemie
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62511
ER  - 
TY  - JOUR
A1  - Sebald, Walter
A1  - Neupert, W.
A1  - Birkmayer, G. D.
T1  - Internal and external contributions to the biogenesis of mitochondrial proteins
N2  - No abstract available
KW  - Biochemie
Y1  - 1970
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62876
ER  - 
TY  - JOUR
A1  - Lindenmaier, W.
A1  - Dittmar, K. E.
A1  - Hauser, H.
A1  - Necker, A.
A1  - Sebald, Walter
T1  - Isolation of a functional human interleukin 2 gene from a cosmid library by recombination in vivo
N2  - A method has been developed that allows the isolation of genomic clones from a cosmid library by homologaus recombination in vivo. This method was used to isolate a human genomic interleukin 2 (IL2) gene. The genomic cosmid library was packaged in vivo into A. phage particles. A recombination-proficient host strain carrying IL2 cDNA sequences in a non-homologaus plasmid vector was infected by the packaged cosmid library. After in vivo packaging and reinfection, recombinants carrying the antibiotic resistance genes of both vectors were selected. From a recombinant cosmid clone the chromosomal IL2 genewas restored. After DNA mediated gene transfer into mouse Ltk- cells human IL2 was expressed constitutively.
KW  - Biochemie
KW  - Recombinant DNA
KW  - DNA mediated gene transfer
KW  - expression plasmid
KW  - screening
KW  - packaging
KW  - bacteriophage lambda
Y1  - 1985
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62662
ER  - 
TY  - JOUR
A1  - Hoppe, J.
A1  - Gatti, D.
A1  - Weber, H.
A1  - Sebald, Walter
T1  - Labeling of individual amino acid residues in the membrane-embedded F\(_0\) part of the F\(_1\) F\(_0\) ATP synthase from Neurospora crassa. Influence of oligomycin and dicyclohexylcarbodiimide
N2  - Three F0 subunits and the F\(_1\) subunit P of the ATP synthase from Neurospora crassa were labeled with the lipophilic photoactivatable reagent 3-(trifluoromethyl)-3-(m-[\(^{125}\)I]iodophenyl)diazirine ([\(^{125}\)I]TID). In the proteolipid subunit which was the most heavily labeled polypeptide labeling was confmed to five residues at the NH2-terminus and five residues at the C-terminus ofthe protein. Labeling occurred at similar positions compared with the homologaus protein (subunit c) in the ATP synthase from Escherichia coli, indicating a similar structure of the proteolipid subunits in their respective organisms. The inhibitors oligomycin and dicyclohexylcarbodiimide did not change the pattern of accessible surface residues in the proteolipid, suggesting that neither inhibitor induces gross conformational changes. However, in the presence of oligomycin, the extent oflabeling in some residues was reduced. Apparently, these residues provide part of the binding site for the inhibitor. After reaction with dicyclohexylcarbodiimide an additional labeled amino acid was found at position 65 corresponding to the invariant carbodümide-binding glutamic acid. These results and previous observations indicate that the carboxyl side chain of Glu-65 is located at the protein-lipid interphase. The idea is discussed that proton translocation occurs at the interphase between different types if F\(_0\) subunits. Dicyclohexylcarbodiimide or oligomycin might disturb this essential interaction between the F\(_0\) subunits.
KW  - Biochemie
Y1  - 1986
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62598
ER  - 
TY  - JOUR
A1  - Sebald, Walter
A1  - Wild, G.
T1  - Mitochondrial ATPase complex from Neurospora crassa
N2  - The A TPase eomplex has been isolated from mitoehondria of N eurospora crassa by immunologieal teehniques. The protein ean be obtained rapidly and qua ntitatively in high purity by miero- or large-seale immunopreeipitation. Immunopreeipitation has been applied to labeled and doubly labeled mitoehondrial proteins in order to investigate the number and moleeular weights of subunit polypeptides , the site of synthesis of subunit polypeptides, and the dieycIohexyIcarbodiimide-binding protein . The A TPase complex obtained by large-seale immunopreeipitation has been used as starting ma terial for the isolation of hydrophobie polypeptides.
KW  - Biochemie
Y1  - 1979
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-82065
ER  - 
TY  - JOUR
A1  - Tzagoloff, A.
A1  - Macino, G.
A1  - Sebald, Walter
T1  - Mitochondrial genes and translation products
N2  - No abstract available
KW  - Biochemie
Y1  - 1979
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-47408
ER  - 
TY  - JOUR
A1  - Kleene, R.
A1  - Pfanner, N.
A1  - Pfaller, R.
A1  - Link, T. A.
A1  - Sebald, Walter
A1  - Neupert, W.
A1  - Tropschug, M.
T1  - Mitochondrial porin of Neurospora crassa: cDNA cloning, in vitro expression and import into mitochondria
N2  - No abstract available
KW  - Biochemie
Y1  - 1987
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62566
ER  - 
TY  - THES
A1  - Kober, Franz-Xaver Wilhelm
T1  - Molecular insights into the protein disulfide isomerase family
T1  - Molekulare Mechanismen der Protein Disulfid Isomerase Familie
N2  - Upon synthesis, nascent polypeptide chains are subject to major rearrangements of their side chains to obtain an energetically more favorable conformation in a process called folding. About one third of all cellular proteins pass through the secretory pathway and undergo oxidative folding in the endoplasmic reticulum (ER). During oxidative folding, the conformational rearrangements are accompanied by the formation of disulfide bonds – covalent bonds between cysteine side chains that form upon oxidation. Protein disulfide isomerase (PDI) assists in the folding of substrates by catalyzing the oxidation of pairs of cysteine residues and the isomerization of disulfide bonds as well as by acting as chaperones. In addition to PDI itself, a family of related ER-resident proteins has formed. All PDI family members share the thioredoxin fold in at least one of their domains and exhibit a subset of the PDI activities. Despite many studies, the role of most PDI family members remains unclear. The project presented in this thesis was aimed to establish tools for the biochemical characterization of single members of the PDI family and their role in the folding process. A combination of fluorescence based assays was developed to selectively study single functions of PDI family members and relate their properties of either catalysis of oxidation or catalysis of isomerization or chaperone activity to the rest of the protein family. A binding assay using isothermal titration calorimetry (ITC) was established to complement the activity assays. Using ITC we could show for the first time that members of the PDI family can distinguish between folded and unfolded proteins selectively binding the latter. The unique information provided by this method also revealed a two-site binding of unfolded proteins by PDI itself. In addition to the functional characterization, experiments were conducted to further investigate the oligomeric state of PDI. We could show that the equilibrium between structurally different states of PDI is heavily influenced by the redox state of the protein and its environment. This new data could help to further our understanding of the interplay between oxidases like PDI and their regenerative enzymes like Ero1, which may be governed by structural changes in response to the change in redox status. Another structural approach was the screening of all investigated PDI family members for suitable crystallization conditions. As a result of this screening we could obtain protein crystals of human ERp27 and were able to solve the structure of this protein with X-ray crystallography. The structure gives insight into the mechanisms of substrate binding domains within the PDI family and helps to understand the interaction of ERp27 with the redox active ERp57. In collaboration with the group of Heike Hermanns we could further show the physiological importance of this interaction under oxidative stress. In conclusion, the project presented in this thesis provides novel tools for an extensive analysis of the activities of single PDI family members as well as a useful set of methods to characterize novel oxidoreductases and chaperones. The initial results obtained with the our novel methods are very promising. At the same time, the structural approach of this project could successfully solve the structure of a PDI family member and give information about the interplay within the PDI family.
N2  - Umlagerungsprozess nennt man Proteinfaltung. Schätzungsweise ein Drittel aller zellulären Proteine werden über den sekretorischen Transportweg geschleust und durchlaufen die oxidative Proteinfaltung im endoplasmatischen Retikulum (ER). Während der oxidativen Faltung werden zusätzlich zur Umlagerung von Seitenketten auch Disulfidbrücken gebildet. Dies sind kovalente Bindungen zwischen Zystein-Seitenketten durch Oxidation entstehen. Protein Disulfid Isomerase (PDI) unterstützt die Faltung von Proteinen im ER indem es die Oxidation zweier Zystein- Seitenketten katalysiert. Neben der Oxidation katalysiert PDI ebenfalls die Isomerisierung von fehlverknüpften Disulfidbrücken und wirkt als Chaperon der Aggregation entgegen. Im Laufe der Evolution hat sich zusätzlich zu PDI eine Gruppe verwandter ER-lokalisierter Proteine gebildet. Diese Mitglieder der PDI-Familie weisen alle das Thioredoxin-Faltungsmotiv in mindestens einer ihrer Domänen auf und besitzen mindestens eine der drei PDI-Aktivitäten. Trotz eingehender Untersuchung ist die Rolle der meisten dieser PDI Familienmitglieder weiterhin unklar. Im Rahmen des Projekts, welches dieser Dissertation zugrunde liegt, wurden Methoden zur biochemischen Charakterisierung einzelner Mitglieder der PDI-Familie, und deren Rolle im Faltungsprozess, entwickelt. Eine Kombination von Fluoreszenzexperimenten wurde etabliert mit der selektiv einzelne Aktivitäten von Faltungshelfern analysiert und qualitativ in die PDI- Familie eingeordnet werde können. Diese fluoreszenzbasierten Methoden wurden durch isothermale Titrationkalorimetrie (ITC) ergänzt. Mit ITC konnten wir als Erste zeigen, dass PDI- Familienmitglieder gefaltete von ungefalteten Proteinen unterscheiden können und letztere selektiv binden. Die zusätzlichen Informationen, die in einem ITC-Experiment gewonnen wurden, zeigten, dass PDI mit Substraten mit Hilfe von zwei unterschiedlichen Bindungsstellen interagiert. Neben der funktionellen Analyse der PDI-Familie wurde Experimente durchgeführt um den oligomeren Zustand von PDI näher zu untersuchen. Wir konnten zeigen, dass das Gleichgewicht zwischen strukturell verschiedenen Zuständen entscheidend vom Redox-Status von PDI abhängt. Diese neuen Daten werfen ein neues Licht auf die Interaktion zwischen Oxidasen wie PDI und ihren regenerativen Enzymen wie Ero1. Diese Interaktion könnte sehr wohl durch strukturelle Veränderungen, ausgelöst durch Redox-Reaktionen, reguliert werden. Als weiteren strukturellen Ansatz zur Erforschung der PDI-Familie wurden alle verwendeten Familienmitglieder auf aussichtsreiche Kristallisationsbedingungen hin untersucht. Durch dieses Screening konnte ERp27 kristallisiert und seine Struktur durch Röntgenkristallografie aufgeklärt werden. Die so gewonnene Struktur gibt Aufschluss über die Mechanismen der Substratbindung in der PDI- Familie und hilft ebenfalls dabei, die Interaktion zwischen ERp27 und dem redoxaktiven ERp57 besser zu verstehen. Auf Grund dieser Daten konnten wir gemeinsam mit der Gruppe von Heike Hermanns die physiologische Bedeutung dieser Interaktion bei oxidativem Stress aufzeigen. Zusammenfassend konnten im Rahmen dieses Projektes neue Werkzeuge zur eingehenden Analyse der PDI-Familie etabliert werden, welche auch zur Charakterisierung neuer Oxidoreduktasen und Chaperone verwendet werden können. Die ersten Ergebnisse die mit Hilfe dieser neuen Methoden gewonnen werden konnten sind vielversprechen. Gleichzeitig konnten wir mit ERp27 die Struktur eines weiteren PDI-Familienmitgliedes lösen und so weitere Einblicke in das komplexe Netzwerk der PDI-Familie gewinnen.
KW  - Biochemie
KW  - Proteinfaltung
KW  - Disulfidbrücken
KW  - Protein Disulfid Isomerase
KW  - Biochemistry
KW  - protein folding
KW  - disulfide bonds
KW  - protein disulfide isomerase
KW  - PDI
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-72144
ER  - 
TY  - JOUR
A1  - Gessler, Manfred
A1  - Bruns, Gail A. P.
T1  - Molecular mapping and cloning of the breakpoints of a chromosome 11p14.1-p13 deletion associated with the AGR syndrome
N2  - Chromosome 11p13 is frequently rearranged in individuals with the WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) or parts of this syndrome. To map the cytogenetic aberrations molecularly, we screened DNA from cell Unes with known WAGR-related chromosome abnormalities for rearrangements with pulsed fleld gel (PFG) analysis using probes deleted from one chromosome 11 homolog of a WAGR patient. The first alteration was detected in a cell line from an individual with aniridia, genitourinary anomalies, mental retardation, and a deletion described as 11p14.1-p13. We have located one breakpoint close to probe HU11-164B and we have cloned both breakpoint sites as well as the junctional fragment. The breakpoints subdivide current intervals on the genetic map, and the probes for both sides will serve as important additional markers for a long-range restriction map of this region. Further characterization and sequencing of the breakpoints may yield insight into the mechanisms by which these deletions occur.
KW  - Biochemie
Y1  - 1988
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59264
ER  - 
TY  - JOUR
A1  - Weigel, U.
A1  - Meyer, M.
A1  - Sebald, Walter
T1  - Mutant proteins of human interleukin 2. Renaturation yield, proliferative activity and receptor binding
N2  - No abstract available
KW  - Biochemie
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62543
ER  - 
TY  - JOUR
A1  - Reusch, P.
A1  - Arnold, S.
A1  - Heusser, C.
A1  - Wagner, K.
A1  - Weston, B.
A1  - Sebald, Walter
T1  - Neutralizing monoclonal antibodies define two different functional sites in human interleukin-4
N2  - Human interleukin-4 (IL-4) is a small four-helix-bundle protein which is essential for organizing defense reactions against macroparasites, in particular helminths. Human IL-4 also appears to exert a pathophysiological role during various IgE-mediated allergic diseases. Seven different monoclonal antibodies neutralizing the activity of human IL-4 were studied in order to identify functionally important epitopes. A collection of 41 purified IL-4 variants was used to analyse how defined amino acid replacements affect binding affinity for each individual mAb. Specific amino acid positions could be assigned to four different epitopes. mAbs recognizing epitopes on helix A and/or C interfered with IL-4 receptor binding and thus inhibited IL-4 function. However, other mAbs also inhibiting IL-4 function recognized an epitope on helix D of IL-4 and did not inhibit IL-4 binding to the receptor protein. One mAb, recognizing N-terminal and C-terminal residues, partially competed for binding to the receptor. The results of these mAb epitope analyses confirm and extend previous data on the functional consequences of the amino acid replacements which showed that amino acid residues in helices A and C of IL-4 provide a binding site for the cloned IL-4 receptor and that a signalling site in helix D interacts with a further receptor protein.
KW  - Biochemie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62418
ER  -