2BAP

Crystal structure of the N-terminal mDia1 Armadillo Repeat Region and Dimerisation Domain in complex with the mDia1 autoregulatory domain (DAD)

Summary for 2BAP

• Entry DOI: 10.2210/pdb2bap/pdb
• Related: 1z2c 2bnx
• Descriptor: Diaphanous protein homolog 1 (2 entities in total)
• Functional Keywords: armadillo repeats, all helical, signaling protein
• Biological source: Mus musculus (house mouse); More
• Cellular location: Cell membrane : O08808 O08808
• Total number of polymer chains: 4
• Total formula weight: 85988.90

Authors

Lammers, M.,Rose, R.,Scrima, A.,Wittinghofer, A. (deposition date: 2005-10-14, release date: 2006-03-07, Last modification date: 2023-08-23)

Primary citation

Lammers, M.,Rose, R.,Scrima, A.,Wittinghofer, A.
The regulation of mDia1 by autoinhibition and its release by Rho*GTP.
Embo J., 24:4176-4187, 2005

PubMed Abstract: 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.

PubMed: 16292343
DOI: 10.1038/sj.emboj.7600879

Experimental method

X-RAY DIFFRACTION (3.3 Å)