Im Zuge der Evolution neuer Proteine werden häufig strukturell autonome Bausteine alter Proteine wiederverwendet und neu kombiniert. Solche Bausteine nennt man Proteindomänen. Diese Arbeit handelt von der Entdeckung von Proteindomänen allein auf der Basis von Sequenzinformation. Es werden fünf Entdeckungen neuer evolutionär mobiler Proteindomänen detailliert beschrieben. Desweiteren werden zwei Anwendungen von Domänenmodellen für die Analyse komplett sequenzierter Genome dargestellt. Diese Analysen lieferten wertvolle neue Einsichten in unterschiedlichste Bereiche der molekularen Zellbiologie, wie der Evolution des Nukleolus, und in menschliche Krankheiten, im besonderen der Entstehung autoinflammatorischer Erbkrankheiten und erblicher Epilepsie.
During the course of evolution, structurally autonomous modules of old proteins are frequently reused and recombined into new proteins. These modules are known as protein domains. This thesis deals with the discovery of previously unknown protein domains based on sequence information alone. Five single discoveries of novel protein domains are described in detail. Furthermore, two applications of models of protein domains in the analysis of completely sequenced genomes are presented. The analyses provided valuable new insights into different aspects of molecular cell biology, in particular the evolution of the nucleolus, and in human hereditary diseases, i.e. autoinflammatory syndromes and epilepsy.
Keywords:
Protein domains, apoptosis, familial mediterranean fever, Spin/Ssty repeat, DAPIN domain, EPTP repeat, CSPG repeat, ITIM, nucleolus evolution, autosomal dominant lateral temporal epilepsy
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Inhaltsverzeichnis
Proteindomänen, Apoptose, Familiäres Mediterranes Fieber, Spin/Ssty-Repeat, DAPIN-Domäne, EPTP-Repeat, CSPG-Repeat, ITIM, Evolution des Nucleolus, autosomal dominante lateral-temporale Epilepsie
Titelblatt, Inhaltsverzeichnis, Abkürzungsverzeichnis (1, I-III)
1 Einleitung (1-13)
2 The DAPIN family: a novel domain links apoptotic and interferon response proteins (14-17)
3 The Spin/Ssty repeat: a new motif in proteins involved in vertebrate development from gamete to embryo (18-24)
4 A novel repeat in the melanoma-associated chondroitin sulfate proteoglycan defines a new protein family (25-30)
5 The novel EPTP repeat defines a superfamily of proteins implicated in epileptic disorders (31-36)
6 Sequence similarity between prokaryotic nitrogen-sensing histidine kinases and vertebrate hypoxia-inducible proteins (37-46)
7 Systematic identification of immunoreceptor tyrosinebased motifs in the human proteome (47-69)
8 Insights into the evolution of the nucleolus by an analysis of its protein domain repertoire (70-110)
9 Diskussion (111-125)
10 Zusammenfassung (126-127)
11 Anhang (A-1 - A-15)
