@article{SebaldHofstoetterHackeretal.1969, author = {Sebald, Walter and Hofst{\"o}tter, T. and Hacker, D. and B{\"u}cher, T.}, title = {Incorporation of amino acids into mitochondrial protein of the flight muscle of Locusta migratoria in vitro and in vivo in the presence of cycloheximide}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62919}, year = {1969}, abstract = {No abstract available}, subject = {Biochemie}, language = {en} } @article{MuellerDieckmannSebaldetal.1994, author = {M{\"u}ller, T. and Dieckmann, T. and Sebald, Walter and Oschkinat, H.}, title = {Aspects of receptor binding and signalling of interleukin-4 investigated by site-directed mutagenesis and NMR spectroscopy}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62444}, year = {1994}, abstract = {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.}, subject = {Biochemie}, language = {en} } @article{SchmittEguWalteretal.2021, author = {Schmitt, T. and Egu, D.T. and Walter, E. and Sigmund, A.M. and Eichkorn, R. and Yazdi, A. and Schmidt, E. and S{\´a}rdy, M. and Eming, R. and Goebeler, M. and Waschke, J.}, title = {Ca\(^{2+}\) signalling is critical for autoantibody-induced blistering of human epidermis in pemphigus}, series = {British Journal of Dermatology}, volume = {185}, journal = {British Journal of Dermatology}, number = {3}, doi = {10.1111/bjd.20091}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262810}, pages = {595 -- 604}, year = {2021}, abstract = {Background Pemphigus is a severe bullous autoimmune skin disease. Pemphigus foliaceus (PF) is characterized by antidesmoglein (Dsg) 1 IgG causing epidermal blistering; mucosal pemphigus vulgaris (mPV) by anti-Dsg3 IgG inducing erosions in the mucosa; and mucocutaneous pemphigus vulgaris (PV) by affecting both, with autoantibodies targeting Dsg1 and Dsg3. Objectives To characterize the Ca\(^{2+}\) flux pathway and delineate its importance in pemphigus pathogenesis and clinical phenotypes caused by different antibody profiles. Methods Immunoprecipitation, Ca\(^{2+}\) flux analysis, Western blotting, immunofluorescence staining, dissociation assays and a human skin ex vivo model were used. Results PV IgG and PF IgG, but neither Dsg3-specific monoclonal antibody (AK23) nor mPV IgG, caused Ca\(^{2+}\) influx in primary human keratinocytes. Phosphatidylinositol 4-kinase α interacts with Dsg1 but not with Dsg3. Its downstream target - phospholipase-C-γ1 (PLC) - was activated by PV IgG and PF IgG but not AK23 or mPV IgG. PLC releases inositol 1,4,5-trisphosphate (IP3) causing IP3 receptor (IP3R) activation and Ca2+ flux from the endoplasmic reticulum into the cytosol, which stimulates Ca2+ release-activated channels (CRAC)-mediated Ca\(^{2+}\) influx. Inhibitors against PLC, IP3R and CRAC effectively blocked PV IgG and PF IgG-induced Ca\(^{2+}\) influx; ameliorated alterations of Dsg1 and Dsg3 localization, and reorganization of keratin and actin filaments; and inhibited loss of cell adhesion in vitro. Finally, inhibiting PLC or IP3R was protective against PV IgG-induced blister formation and redistribution of Dsg1 and Dsg3 in human skin ex vivo. Conclusions Ca2+-mediated signalling is important for epidermal blistering and dependent on the autoantibody profile, which indicates different roles for signalling complexes organized by Dsg1 and Dsg3. Interfering with PLC and Ca\(^{2+}\) signalling may be a promising approach to treat epidermal manifestations of pemphigus.}, language = {en} } @article{WalterCollenburgJaptoketal.2016, author = {Walter, T. and Collenburg, L. and Japtok, L. and Kleuser, B. and Schneider-Schaulies, S. and M{\"u}ller, N. and Becam, J. and Schubert-Unkmeir, A. and Kong, J. N. and Bieberich, E. and Seibel, J.}, title = {Incorporation and visualization of azido-functionalized N-oleoyl serinol in Jurkat cells, mouse brain astrocytes, 3T3 fibroblasts and human brain microvascular endothelial cells}, series = {Chemical Communications}, volume = {52}, journal = {Chemical Communications}, number = {55}, doi = {10.1039/c6cc02879a}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-191263}, pages = {8612-8614}, year = {2016}, abstract = {The synthesis and biological evaluation of azido-N-oleoyl serinol is reported. It mimicks biofunctional lipid ceramides and has shown to be capable of click reactions for cell membrane imaging in Jurkat and human brain microvascular endothelial cells.}, language = {en} } @article{NeupertSebaldSchwabetal.1969, author = {Neupert, W. and Sebald, Walter and Schwab, A. J. and Pfaller, A. and B{\"u}cher, T.}, title = {Puromycin sensitivity of ribosomal label after incorporation of \(^{14}\)C-labelled amino acids into isolated mitochondria from Neurospora crassa}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62899}, year = {1969}, abstract = {Radioactive amino acids were incorporated into isolated mitochondria from Neurospora crassa. Then the mitochondrial ribosomes were isolated and submitted to density gradient centrifugation. A preferential labelling of polysomes was observed. However, when the mitochondrial suspension was treated with puromycin after amino acid incorporation, no radioactivity could be detected in either the monosomes or the polysomes. The conclusion is drawn that isolated mitochondria under these conditions do not incorporate significant amounts of amino acids into proteins of their ribosomes.}, subject = {Biochemie}, language = {en} } @article{SebaldSchwabBuecher1969, author = {Sebald, Walter and Schwab, A. J. and B{\"u}cher, T.}, title = {Cycloheximide resistant amino acid incorporation into mitochondrial protein from Neurospora crassa in vivo}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62900}, year = {1969}, abstract = {No abstract available}, subject = {Biochemie}, language = {en} } @article{SebaldBuecherOlbrichetal.1968, author = {Sebald, Walter and B{\"u}cher, T. and Olbrich, B. and Kaudewitz, F.}, title = {Electrophoretic pattern of and amino acid incorporation in vitro into the insoluble mitochondrial protein of neurospora crassa wild type and mi-1 mutant}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62926}, year = {1968}, abstract = {No abstract available}, subject = {Biochemie}, language = {en} } @article{MerzFliednerLehrnbecheretal.1990, author = {Merz, H. and Fliedner, A. and Lehrnbecher, T. and Sebald, Walter and M{\"u}ller-Hermelink, H. K. and Feller, A. C.}, title = {Cytokine expression in B-cell non-Hodgkin lymphomas}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62539}, year = {1990}, abstract = {No abstract available}, subject = {Biochemie}, language = {en} } @article{KleenePfannerPfalleretal.1987, author = {Kleene, R. and Pfanner, N. and Pfaller, R. and Link, T. A. and Sebald, Walter and Neupert, W. and Tropschug, M.}, title = {Mitochondrial porin of Neurospora crassa: cDNA cloning, in vitro expression and import into mitochondria}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62566}, year = {1987}, abstract = {No abstract available}, subject = {Biochemie}, language = {en} } @article{SebaldGrafLukins1979, author = {Sebald, Walter and Graf, T. and Lukins, H. B.}, title = {The dicyclohexylcarbodiimide-binding protein of the mitochondrial ATPase complex from Neurospora crassa and Saccharomyces cerevisiae. Identification and isolation}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62792}, year = {1979}, abstract = {Incubation of mitochondria from Neuraspara crassa and Saccharomyces cerevisiae with the radioactive ATPase inhibitor [14C]dicyclohexylcarbodiimide results in the irreversible and rather specific labelling of a low-molecular-weight polypeptide. This dicyclohexylcarbodiimide-binding protein is identical with the smallest subunit (Mr 8000) of the mitochondrial ATPase complex, and it occurs as oligomer, probably as hexamer, in the enzyme protein. The dicyclohexylcarbodiimide-binding protein is extracted from whole mitochondria with neutral chloroformjmethanol both in the free and in the inhibitor-modified form. In Neuraspara and yeast, this extraction is highly selective and the protein is obtained in homogeneaus form when the mitochondria have been prewashed with certain organic solvents. The bound dicyclohexylcarbodiimide Iabel is enriched in the purified protein up to 50-fold compared to whole mitochondria. Based on the amino acid analysis, the dicyclohexylcarbodiimide-binding protein from Neurospora and yeast consists of at least 81 and 76 residues, respectively. The content of hydrophobic residues is extremely high. Histidine and tryptophan are absent. The N-terminal ~mino acid is tyrosine in Neuraspara and formylmethionine in yeast.}, subject = {Biochemie}, language = {en} } @article{GrafSebald1978, author = {Graf, T. and Sebald, Walter}, title = {The dicyclohexylcarbodiimide-binding protein of the mitochondrial ATPase complex from beef heart. Isolation and amino acid composition}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62806}, year = {1978}, abstract = {No abstract available}, subject = {Biochemie}, language = {en} } @article{WeissSebaldBuecher1971, author = {Weiss, H. and Sebald, Walter and B{\"u}cher, T.}, title = {Cycloheximide resistant incorporation of amino acids into a polypeptide of the cytochrome oxidase of Neurospora crassa}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62866}, year = {1971}, abstract = {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.}, subject = {Biochemie}, language = {en} } @article{NeupertSebaldSchwabetal.1969, author = {Neupert, W. and Sebald, Walter and Schwab, A. J. and Massinger, P. and B{\"u}cher, T.}, title = {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}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62884}, year = {1969}, abstract = {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.}, subject = {Biochemie}, language = {en} } @article{KruseShenArnoldetal.1993, author = {Kruse, N. and Shen, B. J. and Arnold, S. and Tony, H. P. and M{\"u}ller, T. and Sebald, Walter}, title = {Two distinct functional sites of human interleukin 4 are identified by variants impaired in either receptor binding or receptor activation}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62451}, year = {1993}, abstract = {Interleukin 4 (IL-4) exerts a decisive role in the coord.ination of proteelive immune responses against parasites, particularly helminths. A disregulation of ll.r4 function is possibly involved in the genesis of allergic disease states. The search for important amino acid residues in human ll.r4 by mutational analysis of charged invariant amino acid positions identified two distinct functional sites in the 4-helix-bundle protein. Site 1 was marked by amino acid substitutions of the glutamic acid at position 9 in helix A and arginine at position 88 in helix C. Exchanges at both positions led to IL-4 variants deficient in binding to the extracellular domain of the ll.r4 receptor (IL-4ReJ. In parallel, up to 1000-fold increased concentrations of this type of variant were required to induce T -cell proliferation and B-eeil CD23 expression. Site 2 was marked by amino acid exchanges in helix D at positions 121, 124 and 125 (arginine, tyrosine and serine respectively in the wild-type).ß.A variants affected at site 2 exhibited partial agonist activity during T -cell proliferation; however, they still bound with high affinity to IL-4Rex. [The generation of an IL-4 antagonist by replacing tyrosine 124 with aspartic acid has been described before by Kruse et al. (1992) (EMBO }., 11, 3237-3244)]. These findings indicate that IL-4 functions by bind.ing IL-4Rex via site 1 which is constituted by residues on helices A and C. They further suggest that the association of a second, still undetined receptor protein with site 2 in helix D activates the receptor system and generates a transmembrane signal.}, subject = {Biochemie}, language = {en} } @article{LehrnbecherMerzSebaldetal.1991, author = {Lehrnbecher, T. and Merz, H. and Sebald, Walter and Poot, M.}, title = {Interleukin 4 drives phytohemagglutinin-activated T cells through several cell cycles: no synergism between interleukin 2 and interleukin 4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62491}, year = {1991}, abstract = {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.}, subject = {Biochemie}, language = {en} } @article{MerzFliednerOrschescheketal.1991, author = {Merz, H. and Fliedner, A. and Orscheschek, K. and Binder, T. and Sebald, Walter and M{\"u}ller-Hermelink, H. K. and Feller, A. C.}, title = {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}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62483}, year = {1991}, abstract = {No abstract available}, subject = {Biochemie}, language = {en} } @article{KruseLehrnbecherSebald1991, author = {Kruse, N. and Lehrnbecher, T. and Sebald, Walter}, title = {Site-directed mutagenesis reveals the importance of disulfide bridges and aromatic residues for structure and proliferative activity of human interleukin-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62505}, year = {1991}, abstract = {Mutant proteins (muteins) of human lnterleukin-4 (llA) were constructed by means of in vitro mutagenesis. The muteins were expressed in E. co/1, submitted to a renaturation and purification protocol and analysed for biological activity. Exchange of the cysteines at either position 46 or 99 which form one of the three disulfide bridges resulted. in a nearly co•mplete loss · of biological actiyity and an unstable protein. The exchange of tyrosine 124 also inactivated the protein, while a mutation of tyrosine 56 left some residual activity. Exchange of the other four cysteines or of · the single tryptophane had smaller etTects.}, subject = {Biochemie}, language = {en} } @article{MuellerSebaldOschkinat1994, author = {M{\"u}ller, T. and Sebald, Walter and Oschkinat, H.}, title = {Antagonist design through forced electrostatic mismatch}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62408}, year = {1994}, abstract = {No abstract available}, subject = {Biochemie}, language = {en} } @article{DemchukMuellerOschkinatetal.1994, author = {Demchuk, E. and Mueller, T. and Oschkinat, H. and Sebald, Walter and Wade, R. C.}, title = {Receptor binding properties of four-helix-bundle growth factors deduced from electrostatic analysis}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62424}, year = {1994}, abstract = {Hormones of the hematopoietin class mediate signal transduction by binding to specific transmembrane receptors. Structural data show that the human growth hormone (hGH) forms a complex with a homodimeric receptor and that hGH is a member of a class of hematopoietins possessing an antiparallel 4-a-helix bundle fold. Mutagenesis experiments suggest that electrostatic interactions may have an important influence on hormonereceptor recognition. In order to examine the specificity of hormone-receptor complexation, an analysis was made of the electrostatic potentials of hGH, interleukin-2 (IL-2), interleukin-4 (IL-4), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and the hGH and IL-4 receptors. The binding surfaces of hGH and its receptor, and of IL-4 and its receptor, show complementary electrostatic potentials. The potentials of the hGH and its receptor display approximately 2-fold rotational symmetry because the receptor subunits are identical. In contrast, the potentials of GM-CSF and IL-2 Iack such symmetry, consistent with their known high affinity for hetero-oligomeric receptors. Analysis of the electrostatic potentials supports a recently proposed hetero-oligomeric model for a high-affinity IL-4 receptor and suggests a possible new receptor binding mode for G-CSF; it also provides valuable information for guiding structural and mutagenesis studies of signal-transducing proteins and their receptors.}, subject = {Biochemie}, language = {en} } @article{LehrnbecherPootOrschescheketal.1994, author = {Lehrnbecher, T. and Poot, M. and Orscheschek, K. and Sebald, Walter and Feller, A. C. and Merz, H.}, title = {Interleukin 7 as interleukin 9 drives phytohemagglutinin-activated T cells through several cell cycles; no synergism between interleukin 7, interleukin 9 and interleukin 4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62438}, year = {1994}, abstract = {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.}, subject = {Biochemie}, language = {en} }