Zusammenfassung:
Die extrazelluläre Matrix von Myxococcus xanthus ist ein essentieller Bestandteil für ein funktionelles Typ-IV-Pili-abhängiges Bewegungssystem sowie für den kontrollierten Ablauf des charakteristischen Entwicklungs-programms in nährstoffarmer Umgebung. Die korrekte Zusammensetzung der extrazellulären Matrix wird über Proteine von Zwei-Komponenten-Systemen einschließlich des verwaisten Antwortregulators DigR reguliert.
Im Rahmen dieser Dissertation wurde die verwaiste Hybrid-Histidinkinase SgmT charakterisiert und als korrespondierender Partner von DigR identifiziert. Neben einer Kinase- und einer Empfängerdomäne besitzt SgmT eine N-terminale GAF-Domäne und eine C-terminale GGDEF-Domäne. Mit Hilfe genetischer und biochemischer Analysen wurde die Funktion der einzelnen Domänen von SgmT untersucht, wobei die GAF-Domäne als sensorische Haupteinheit fungiert und die Kinaseaktivität von SgmT steuert. Die GGDEF-Domäne ist ein Rezeptor für den sekundären Botenstoffs c-di-GMP, der SgmT abhängig von dessen Bindung zellulär lokalisiert. Desweiteren wurde eine DigR-Bindestelle im Promoter von fibA identifiziert, einem Gen, das für eine extrazelluläre Matrixprotease kodiert. Die Identifikation weiterer DigR-Bindestellen in den Promotorregionen von signifikant-regulierten Genen aus vergleichenden Transkriptomstudien lässt vermuten, dass das SgmT/DigR-Regulon aus Genen besteht, die für sekretierte Proteine sowie für Enzyme des Sekundärmetabolismus kodieren. Diese Beobachtungen geben Grund zur Annahme, dass SgmT und DigR die Zusammensetzung der extrazellulären Matrix direkt regulieren, und dass die Funktion von SgmT über zwei sensorische Domänen gesteuert wird, wobei die Kinaseaktivität durch Ligandenbindung an die GAF-Domäne und die zelluläre Lokalisierung von SgmT über die Bindung von c-di-GMP an die GGDEF-Domäne reguliert wird.
Desweiteren wurden konservierte c-di-GMP-abhängige Proteine in M. xanthus identifiziert und damit begonnen deren Einfluss auf wichtige zelluläre Prozesse hin zu untersuchen. Darüber hinaus wurden erste Erkenntnisse gewonnen, dass c-di-GMP möglicherweise an der Koordination des Entwicklungsprogramms beteiligt sein könnte.
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