@article{ArgosDandekar1994,
  author    = {Argos, P. and Dandekar, Thomas},
  title     = {Delineating the main chain topology of four-helix bundle proteins using the genetic algorithm and knowledge based on the amino acid sequence alone},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-33807},
  year      = {1994},
  abstract  = {No abstract available},
  subject      = {Proteine},
  language  = {en}
}
@phdthesis{Knoop2006,
  author    = {Knoop, Thomas},
  title     = {Auslandsbanken in Deutschland - Theoretische und empirische Analysen {\"u}ber Markteintritt, Gesch{\"a}ftsentwicklung sowie strategische Positionierungsalternativen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-24232},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2006},
  abstract  = {Auslandsbanken gewinnen in Deutschland eine immer gr{\"o}ßere Bedeutung. Obgleich der von der Bundesbank ausgewiesene Marktanteil ausl{\"a}ndischer Banken noch immer im Vergleich zu anderen europ{\"a}ischen L{\"a}ndern unterdurchschnittlich stark ausgepr{\"a}gt ist, messen ihnen deutsche Bankiers eine hohe Wettbewerbsf{\"a}higkeit zu und warnen vor den Folgen einer „Eroberung" ihrer inl{\"a}ndischer Kreditinstitute. Erstmals werden die neu erstarkten Wettbewerber aus den anderen europ{\"a}ischen Nationen sowie den USA im Rahmen der vorliegenden Arbeit umfassend und vor dem Hintergrund der sich ver{\"a}ndernden technologischen und regulativen Rahmenbedingungen analysiert. Hierbei sind die Fragen, weshalb sie in den deutschen Markt eingetreten sind, welche Entwicklungspfade sie eingeschlagen haben und inwieweit ihr Engagement als erfolgreich zu bewerten ist, die zentralen Gesichtspunkte des ersten Abschnitts. Im Gegensatz zu vorangegangenen Arbeiten beschr{\"a}nkt sich der hier gew{\"a}hlte Ansatz nicht auf einen kurzen Zeitraum oder die bloße Analyse des Marketing-Mixes aus Produkt-, Preis- oder Kommunikationspolitik. Vielmehr werden beobachtbare Entwicklungen nicht nur beschrieben, sondern auch auf Basis empirischer Untersuchungen sowie theoretischer {\"U}berlegungen erkl{\"a}rt. Zu Beginn steht hierbei die Frage nach den Eintrittsmotiven, die ausl{\"a}ndische Banken bewogen haben, Niederlassungen in der Bundesrepublik zu er{\"o}ffnen. W{\"a}hrend derartige Studien f{\"u}r andere L{\"a}nder bereits seit l{\"a}ngerem bestehen, k{\"o}nnen erstmals im Rahmen der vorliegenden Arbeit Faktoren herausgearbeitet werden, die Eintrittsentscheidungen offensichtlich signifikant beeinflussen. So best{\"a}tigt sich in diesem Zusammenhang zun{\"a}chst die Bedeutung der bilateralen Wirtschaftsbeziehungen, die mit zunehmender Intensit{\"a}t die Gr{\"u}ndungsneigung erh{\"o}hen. F{\"u}r die Bundesrepublik zeigt sich jedoch auch, daß eine {\"u}berdurchschnittliche wirtschaftliche Dynamik einen positiven Einfluß in Bezug auf die Anzahl der Gr{\"u}ndungen aus{\"u}bt, w{\"a}hrend den am Kapitalmarkt herrschenden Bedingungen kein signifikanter Einfluß auf die Eintrittsentscheidungen nachgewiesen werden kann. Die Frage der nachfolgenden Entwicklung wird vor dem Hintergrund eines eher wirtschaftshistorischen Ansatzes beantwortet. Hierbei kristallisiert sich ein homogener Entwicklungspfad heraus, an dessen Beginn Firmenkunden gleicher Herkunft betreut werden und dessen Ende durch den Eintritt in den Wettbewerb um deutsche Privatkunden markiert wird. Der Erfolg ausl{\"a}ndischer Banken in Deutschland wird im weiteren ausf{\"u}hrlich thematisiert. Zun{\"a}chst kann in diesem Zusammenhang gezeigt werden, daß bis zum Jahr 1999 die auf Hymer zur{\"u}ckgehende Liabilities-of-Foreignness-Hypothese f{\"u}r Auslandsbanken in Deutschland best{\"a}tigt werden kann. Seit der Jahrtausendwende lassen sich jedoch keine wesentlichen Rentabilit{\"a}tsunterschiede zwischen in- und ausl{\"a}ndischen Instituten mehr beobachten, wobei es zu beachten gilt, daß die Angleichung der Bankengruppe im wesentlichen auf Verschlechterungen bei den inl{\"a}ndischen Instituten zur{\"u}ckzuf{\"u}hren ist. Anschließend wird der Frage nachgegangen, welche Einfl{\"u}sse f{\"u}r Unterschiede bei der Rentabilit{\"a}t ausl{\"a}ndischer Banken verantwortlich gemacht werden k{\"o}nnen. {\"U}ber die Ansatzpunkte vorangegangener Studien hinaus wird in diesem Zusammenhang ausdr{\"u}cklich die Rolle einer produkt- beziehungsweise kundenorientierten Ausrichtung im Sinne des strategischen Managements ber{\"u}cksichtigt. So zeigt sich, daß neben den bilateralen Wirtschaftsbeziehungen als einzig konstanter Einflußfaktor die Fokussierung einer Bank Effizienzunterschiede erkl{\"a}ren kann. Aufbauend auf diesen Erkenntnissen wendet sich der zweite Abschnitt der Frage zu, welche strategischen Positionierungsm{\"o}glichkeiten sich einer ausl{\"a}ndischen Bank in Deutschland bieten. Vorangegangene Arbeiten zum strategischen Bankmanagement befassen sich in diesem Zusammenhang vornehmlich mit der Ausrichtung nationaler Wettbewerber oder diskutieren Internationalisierungsstrategien aus Sicht der Muttergesellschaft eines multinationalen Bankkonzerns. Der hier verfolgte Ansatz unterscheidet sich dahingehend, daß ausgehend von einem Marktimperativ die Positionierung der Tochtergesellschaft im Zentrum steht. Hierbei gewinnt die Frage nach der Transferierbarkeit von wettbewerbsrelevanten Ressourcen eine zentrale Bedeutung, da im Sinne des Resource-Based Views derartige Kompetenzen {\"u}ber die F{\"a}higkeit zur Besetzung attraktiver Positionen entscheiden. Neben nat{\"u}rlichen Barrieren, die eine grenz{\"u}berschreitende Nutzung von bestehenden Infrastruktureinrichtungen beziehungsweise von im Heimatland gewonnenen Kundeninformationen verhindern, sind es in erster Linie regulative und kulturelle Barrieren, die einen maßgeblichen Einfluß auf die Positionierungsalternativen ausl{\"a}ndischer Banken in Deutschland aus{\"u}ben. Aufbauend auf dem Positionierungsansatz von Dombret und Kern zeigt sich in diesem Zusammenhang, daß vornehmlich produktbezogene Kompetenzen als erfolgversprechende Ansatzpunkte f{\"u}r ausl{\"a}ndische Banken dienen.},
  subject      = {Allfinanz},
  language  = {de}
}
@phdthesis{PatinoGonzalez2007,
  author    = {Pati{\~n}o Gonzalez, Edwin},
  title     = {Functional Studies and X-Ray Structure Analysis of Human Interleukin-5 Receptor Alpha and Human Interleukin-5 Complex},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-27319},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {Interleukin-5 (IL-5) is a member of the hematopoietic class I cytokines and is specifically involved in eosinophil activation. IL-5 plays an important role in disease conditions such as allergic asthma and other hypereosinophilias, which are characterized by highly increased levels of eosinophils in peripheral blood and tissues. The IL-5 receptor is a heterodimer consisting of a binding alpha subunit (IL- 5R\&\#945;) and a common beta subunit (IL-5R\&\#946;). This IL-5R\&\#946; is shared with the IL-3 and GM-CSF receptors. The IL-5R\&\#945; is required for ligand-specific binding, whereas the association of the IL-5R\&\#946; subunit triggers intracellular signal transduction. Previous studies have described the crystallographic structure of human IL-5 (hIL-5), as well as that of the common IL-5R\&\#946; chain (IL-5R\&\#946;c) However, no experimental structural data are yet available for the interaction of the high-affinity IL-5 receptor IL-5R\&\#945; with its ligand IL-5. Therefore, this thesis had the principle objective to gain new insights into the basis of this important agonist-receptor interaction. In particular, data on the recombinant expression, purification and preparation of the binary complex of hIL-5 bound to the receptor ectodomain of hIL-5R\&\#945; are shown, as well as the subsequent crystal structure analysis of the binary ligand-receptor (hIL-5R\&\#945;/hIL-5) complex. Both proteins were expressed in an Escherichia coli expression system, purified to homogeneity, and crystallized. However, since the initial analysis of these crystals did not show any X-ray diffraction, each step of the preparation and crystallization procedure had to be stepwise optimized. Several improvements proved to be crucial for obtaining crystals suitable for structure analysis. A free cysteine residue in the N-terminal domain of the hIL-5R\&\#945; ectodomain protein was mutated to alanine to remove protein heterogeneity. In addition, hIL-5 affinity chromatography of the receptor protein proved to be absolutely crucial for crystal quality. Additive screening using the initial crystallization condition finally yielded crystals of the binary complex, which diffracted to 2.5{\AA} resolution and were suitable for structure analysis. The preliminary structure data demonstrate a new receptor architecture for the IL-5R\&\#945; ligand-binding domain, which has no similarities to other cytokine class I receptor structures known so far. The complex structure demonstrates that the ligand-binding region of human IL-5R\&\#945; is dispersed over all three extracellular domains, and adopts a binding topology in which the cytokine recognition motif (CRM) needs the first Fn-III domain of the human IL-5R\&\#945; to bind the ligand. In a second project, a prokaryotic expression system for murine IL-5 (mIL-5) was established to allow the production of mIL-5 and mIL-5 antagonist that should facilitate functional studies in mice. Since the expression of mIL-5 in E. coli had never been successful so far, a fusion protein system was generated expressing high yields of mIL-5. Chemical cleavage with cyanogen bromide (CNBr) was used to release mIL-5 monomers, which were subsequently purified and refolded. This technique yielded an active murine IL-5 dimer as confirmed by TF-1 cell proliferation assays. The protein was crystallized and the structure of mIL-5 could be determined at 2.5{\AA} resolution. The molecular structure revealed a symmetrical left-handed four helices bundle dimer similar to human IL-5. Analysis of the structure-/function relationship allowed us to design specific mIL-5 antagonist molecules, which are still under examination. Taken together, these findings provide further insights in the IL-5 and IL-5R interaction which may help to further understand and depict this and other cytokine-receptor interactions of similar architecture, e.g. the IL-13 ligand-receptor system. Ultimately, this may represent another piece of puzzle in the attempts to rationally design and engineer novel IL-5-related pharmacological therapeutics.},
  subject      = {Functional Studies},
  language  = {en}
}
@phdthesis{Delto2015,
  author    = {Delto, Carolyn Francesca},
  title     = {Structural and Biochemical Characterization of the GABA(A) Receptor Interacting Protein Muskelin},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115922},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2015},
  abstract  = {In a study from 2011, the protein muskelin was described as a central coordinator of the retrograde transport of GABA(A) receptors in neurons. As muskelin governs the transport along actin filaments as well as microtubules, it might be the first representative of a novel class of regulators, which coordinate cargo transport across the borders of these two independent systems of transport paths and their associated motorproteins. To establish a basis for understanding the mode of operation of muskelin, the aim of this thesis was an in-depth biochemical and structural characterization of muskelin and its interaction with the GABA(A) receptor. One focus of the work was the analysis of the oligomerization of muskelin. As could be demonstrated, the oligomerization is based on two independent interactions mediated by different domains of the protein: a known interaction of the N-terminal discoidin domain with the C-terminal portion, termed head-to-tail interaction, and a dimerization of the LisH motif in muskelin that was so far neglected in the literature. For the detailed studies of both binding events, the solution of a crystal structure of a fragment of muskelin, comprising the Discoidin domain and the LisH motif, was an important basis. The fragment crystallized as a dimer, with dimerization being mediated solely by the LisH motif. Biochemical analysis corroborated that the LisH motif in muskelin serves as a dimerization element, and, moreover, showed that the C-terminal domain of the protein substantially stabilizes this dimerization. In addition, the crystal structure revealed the molecular composition of the surface of the head in the head-to-tail interaction, namely the discoidin domain. This information enabled to map the amino acids contributing to binding, which showed that the binding site of the head-to-tail interaction coincides with the generic ligand binding site of the discoidin domain. As part of the analyses, residues that are critical for LisH-dimerization and the head-to-tail binding, respectively, were identified, whose mutation specifically interfered with each of the interactions separately. These mutations allowed to investigate the interplay of these interactions during oligomerization. It could be shown that recombinant muskelin assembles into a tetramer to which both interactions, the LisH-dimerization and the head-to-tail binding, contribute independently. When one of the two interactions was disturbed, only a dimer mediated via the respective other interaction could be formed; when both interactions were disturbed, the protein was present as monomer. Furthermore, Frank Heisler in the group of Matthias Kneussel was able to show the drastic impact of an impaired LisH-dimerization on muskelin in cells using these mutations. Disturbing the LisH-dimerization led to a complete redistribution of the originally cytoplasmic muskelin to the nucleus which was accompanied by a severe impairment of its function during GABA(A) receptor transport. Following up on these results in an analysis of muskelin variants, for which alterations of the subcellular localization had been published earlier, the crucial influence of LisH-dimerization to the subcellular localization and thereby the role of muskelin in the cell was confirmed. The biochemical studies of the interaction of muskelin and the alpha1 subunit of the GABA(A) receptor demonstrated a direct binding with an affinity in the low micromolar range, which is mediated primarily by the kelch repeat domain in muskelin. For the binding site on the GABA(A) receptor, it was confirmed that the thirteen most C-terminal residues of the intracellular domain are critical for the binding of muskelin. In accordance with the strong conservation of these residues among the alpha subunits of the GABA(A) receptor, it could be shown that an interaction with muskelin in vitro is also possible for the alpha2 and alpha5 subunits. Based on the comparison of the binding sites between the homologous subunits, tentative conclusions can be drawn about the details of the binding, which may serve as a starting point for follow-up studies. This thesis thereby makes valuable contributions to the understanding of muskelin, in particular the significance of its oligomerization. It furthermore provides an experimental framework for future studies that address related topics, such as the characterization of other muskelin interaction partners, or the questions raised in this work.},
  subject      = {Oligomerisation},
  language  = {en}
}