Structure of the autoinhibitory switch in formin mDia1

Structure. 2006 Feb;14(2):257-63. doi: 10.1016/j.str.2005.12.003.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Calorimetry
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism
  • Crystallography, X-Ray
  • Formins
  • Models, Molecular*
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Sequence Alignment
  • rho GTP-Binding Proteins / chemistry*


  • Carrier Proteins
  • Diap1 protein, mouse
  • Formins
  • rho GTP-Binding Proteins

Associated data

  • PDB/2F31