| First Author | Nezami AG | Year | 2006 |
| Journal | Structure | Volume | 14 |
| Issue | 2 | Pages | 257-63 |
| PubMed ID | 16472745 | Mgi Jnum | J:247435 |
| Mgi Id | MGI:5927317 | Doi | 10.1016/j.str.2005.12.003 |
| Citation | Nezami AG, et al. (2006) Structure of the autoinhibitory switch in formin mDia1. Structure 14(2):257-63 |
| abstractText | 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. |
