2bap
From Proteopedia
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Crystal structure of the N-terminal mDia1 Armadillo Repeat Region and Dimerisation Domain in complex with the mDia1 autoregulatory domain (DAD)
Overview
Formins induce the nucleation and polymerisation of unbranched actin, filaments via the formin-homology domains 1 and 2. Diaphanous-related, formins (Drfs) are regulated by a RhoGTPase-binding domain situated in the, amino-terminal (N-terminal) region and a carboxy-terminal, Diaphanous-autoregulatory domain (DAD), whose interaction stabilises an, autoinhibited inactive conformation. Binding of active Rho releases DAD, and activates the catalytic activity of mDia. Here, we report on the, interaction of DAD with the regulatory N-terminus of mDia1 (mDia(N)) and, its release by Rho*GTP. We have defined the elements required for tight, binding and solved the three-dimensional structure of a complex between an, mDia(N) construct and DAD by X-ray crystallography. The core DAD region is, an alpha-helical peptide, which binds in the most highly conserved region, of mDia(N) using mainly hydrophobic interactions. The structure suggests a, two-step mechanism for release of autoinhibition whereby Rho*GTP, although, having a partially nonoverlapping binding site, displaces DAD by ionic, repulsion and steric clashes. We show that Rho*GTP accelerates the, dissociation of DAD from the mDia(N)*DAD complex.
About this Structure
2BAP is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
Reference
The regulation of mDia1 by autoinhibition and its release by Rho*GTP., Lammers M, Rose R, Scrima A, Wittinghofer A, EMBO J. 2005 Dec 7;24(23):4176-87. Epub 2005 Nov 17. PMID:16292343
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