The regulation of mDia1 by autoinhibition and its release by Rho•GTP

摘要: Formins induce the nucleation and polymerisation of unbranched actin filaments via formin-homology domains 1 2. Diaphanous-related formins (Drfs) are regulated by a RhoGTPase-binding domain situated in amino-terminal (N-terminal) region carboxy-terminal Diaphanous-autoregulatory (DAD), whose interaction stabilises an autoinhibited inactive conformation. Binding active Rho releases DAD activates catalytic activity mDia. Here, we report on with regulatory N-terminus mDia1 (mDiaN) its release Rho•GTP. We have defined elements required for tight binding solved three-dimensional structure complex between mDiaN construct X-ray crystallography. The core is α-helical peptide, which binds most highly conserved using mainly hydrophobic interactions. suggests two-step mechanism autoinhibition whereby Rho•GTP, although having partially nonoverlapping site, displaces ionic repulsion steric clashes. show that Rho•GTP accelerates dissociation from mDiaN•DAD complex.