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Projekt
Mechanistic Aspects of Actin Polymerization at WH2-proteins: Human Spir and VopF from V. cholerae in Comparison
Antragsteller
Professor Dr. Kornelius Zeth
Fachliche Zuordnung
Zellbiologie
Förderung
Förderung von 2010 bis 2014
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 171084014
Initiation of actin nucleation and polymerization requires protein scaffolds of different types which allow for sequestration and orientation of free actin molecules. The Arp2/3 complex has been reported to polymerize branched actin filaments, while formin-like nucleators are known to form unbranched actin polymers at the barbed end. A third factor, Spir, has been described to initiate unbranched actin filaments from the pointed end by the occurrence of four subsequent WASP Homology 2 domains (WH2). Due to the localization of Spir at membrane surfaces, a possible function of this protein in vesicle transport within cells has been proposed. The Spir sequence comprises four domains, the KIND domain, the WH2 cluster, the Spir-box and the FYVE domain for membrane interaction. Attachment of Spir to membranes and initiation of actin polymerization processes involves a number of co-factors: actin monomers, formin, and possibly membrane-bound GTPases. To understand the regulation of nucleation and polymerization by Spir on a mechanistic basis we have started to map interactions by structure biology methods. Our first attempt was the determination of a complex structure between the Spir/KIND and the formin Spir interaction (FSI) module. More recently it turned out that also pathogenic bacteria use WH2- domain clusters in secreted effector proteins to manipulate the host cell cytoskeleton. We currently investigate the structure of VopF from Vibrio cholerae mimicking the WH2-scaffold of Spir proteins. Here we aim to understand the interference into the host cell pathways and to compare principles of actin filament formation on WH2 domain clusters in general.
DFG-Verfahren
Schwerpunktprogramme
Internationaler Bezug
Spanien
