2F31

Crystal structure of the autoinhibitory switch in Formin mDia1; the DID/DAD complex

Summary for 2F31

• Entry DOI: 10.2210/pdb2f31/pdb
• Related: 1UX4 1UX5 1V9D 1Y64 1Z2C 2BNX
• Descriptor: Diaphanous protein homolog 1 (3 entities in total)
• Functional Keywords: formin, mdia1, protein-protein complex, armadillo repeats, structural protein
• Biological source: Mus musculus (house mouse); More
• Cellular location: Cell membrane : O08808 O08808
• Total number of polymer chains: 2
• Total formula weight: 28703.99

Authors

Nezami, A.G.,Poy, F.,Eck, M.J. (deposition date: 2005-11-18, release date: 2006-05-30, Last modification date: 2024-02-14)

Primary citation

Nezami, A.G.,Poy, F.,Eck, M.J.
Structure of the Autoinhibitory Switch in Formin mDia1
Structure, 14:257-263, 2006

PubMed Abstract: Diaphanous-related formins (DRFs) regulate the nucleation and polymerization of unbranched actin filaments. The activity of DRFs is inhibited by an intramolecular interaction between their N-terminal regulatory region and a conserved C-terminal segment termed the Diaphanous autoinhibitory domain (DAD). Binding of GTP bound Rho to the mDia1 N terminus releases this autoinhibitory restraint. Here, we describe the crystal structure of the DAD segment of mDia1 in complex with the relevant N-terminal fragment, termed the DID domain. The structure reveals that the DAD segment forms an amphipathic helix that binds a conserved, concave surface on the DID domain. Comparison with the structure of the mDia1 N terminus bound to RhoC suggests that release of the autoinhibitory DAD interaction is accomplished largely by Rho-induced restructuring of the adjacent GTPase binding subdomain (GBD), but also by electrostatic repulsion and a small, direct steric occlusion of the DAD binding cleft by Rho itself.

PubMed: 16472745
DOI: 10.1016/j.str.2005.12.003

Experimental method

X-RAY DIFFRACTION (2.1 Å)