|3dad, resolution 2.30Å ()|
|Gene:||FHOD1, FHOS, FHOS1 (Homo sapiens)|
Crystal structure of the N-terminal regulatory domains of the formin FHOD1
Formins induce the nucleation and polymerization of unbranched actin filaments. They share three homology domains required for profilin binding, actin polymerization, and regulation. Diaphanous-related formins (DRFs) are activated by GTPases of the Rho/Rac family, whose interaction with the N-terminal formin domain is thought to displace a C-terminal Diaphanous-autoregulatory domain (DAD). We have determined the structure of the N-terminal domains of FHOD1 consisting of a GTPase-binding domain (GBD) and the DAD-recognition domain FH3. In contrast to the formin mDia1, the FHOD1-GBD reveals a ubiquitin superfold as found similarly in c-Raf1 or PI3 kinase. This GBD is recruited by Rac and Ras GTPases in cells and plays an essential role for FHOD1-mediated actin remodeling. The FHOD1-FH3 domain is composed of five armadillo repeats, similarly to other formins. Mutation of one residue in the predicted DAD-interaction surface efficiently activates FHOD1 in cells. These results demonstrate that DRFs have evolved different molecular solutions to govern their autoregulation and GTPase specificity.
The human formin FHOD1 contains a bipartite structure of FH3 and GTPase-binding domains required for activation., Schulte A, Stolp B, Schonichen A, Pylypenko O, Rak A, Fackler OT, Geyer M, Structure. 2008 Sep 10;16(9):1313-23. PMID:18786395
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
- Schulte A, Stolp B, Schonichen A, Pylypenko O, Rak A, Fackler OT, Geyer M. The human formin FHOD1 contains a bipartite structure of FH3 and GTPase-binding domains required for activation. Structure. 2008 Sep 10;16(9):1313-23. PMID:18786395 doi:10.1016/j.str.2008.06.008
- Schulte A, Rak A, Pylypenko O, Ludwig D, Geyer M. Purification, crystallization and preliminary structural characterization of the N-terminal region of the human formin-homology protein FHOD1. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Oct 1;63(Pt, 10):878-81. Epub 2007 Sep 19. PMID:17909294 doi:10.1107/S1744309107043400