3DAD

Crystal structure of the N-terminal regulatory domains of the formin FHOD1

Summary for 3DAD

• Entry DOI: 10.2210/pdb3dad/pdb
• Descriptor: FH1/FH2 domain-containing protein 1 (2 entities in total)
• Functional Keywords: formin, fhod1, gtpase-binding domain, ubiquitin-superfold, armadillo repeats, actin-binding, coiled coil, cytoplasm, cytoskeleton, phosphoprotein, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q9Y613
• Total number of polymer chains: 2
• Total formula weight: 74546.53

Authors

Schulte, A.,Stolp, B.,Schonichen, A.,Pylypenko, O.,Rak, A.,Fackler, O.T.,Geyer, M. (deposition date: 2008-05-29, release date: 2008-09-16, Last modification date: 2024-02-21)

Primary citation

Schulte, A.,Stolp, B.,Schonichen, A.,Pylypenko, O.,Rak, A.,Fackler, O.T.,Geyer, M.
The Human Formin FHOD1 Contains a Bipartite Structure of FH3 and GTPase-Binding Domains Required for Activation.
Structure, 16:1313-1323, 2008

PubMed Abstract: 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.

PubMed: 18786395
DOI: 10.1016/j.str.2008.06.008

Experimental method

X-RAY DIFFRACTION (2.3 Å)