Project Details
Projekt
Structure-function analysis of mammalian formins FMNL1 and FMNL2
Applicant
Professor Dr. Matthias Geyer
Subject Area
Cell Biology
Term
from 2010 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 170435620
Regulation of the actin cytoskeleton is a key process for the stability and motility of eukaryotic cells. A diverse family of formin proteins and WH2 domain containing proteins have recently been recognized as actin nucleators and potent polymerization factors of actin filaments. Formins are defined by the presence of a formin homology 2 (FH2) domain, yet, the modular domain architecture appears significantly different for the eight formin families found in man. This research project focuses on the biochemical and structural analysis of the regulatory domains of mammalian formins. The formin-related gene in leukocytes 2 (FMNL2) is myristoylated, an N-terminal lipid modification which targets a protein to cellular membranes. In preliminary work, we have established an in vitro myristoylation assay that allows characterization of FMNL2 in its native form. We plan to analyse how activation by triphosphate Cdc42 influences the conformation of the myristate in the presence of liposomes. Structural analysis of the lipidated protein will be performed and the interaction with the C-terminal autoregulation domain analysed. Also, we are able to purify a complex of the N- and C-terminal domains of FMNL2 which constitute a double homodimer of 58 kDa and 54 kDa. Finally, functional experiments will address the impact of tropomyosin on filament stabilization during elongation.
DFG Programme
Priority Programmes
