PDBsum entry 2bap

Signaling protein

PDB id: 2bap

Contents

Protein chains

294 a.a. *

16 a.a. *

* Residue conservation analysis

PDB id:

2bap

Name:

Signaling protein

Title:

Crystal structure of the n-terminal mdia1 armadillo repeat region and dimerisation domain in complex with the mdia1 autoregulatory domain (dad)

Structure:

Diaphanous protein homolog 1. Chain: b, a. Fragment: mdia1 n-terminal regulatory domain. Synonym: diaphanous-related formin 1, drf1, mdia1, p140mdia. Engineered: yes. Diaphanous protein homolog 1. Chain: d, c. Fragment: mdia1 autoregulatory domain, dad. Synonym: diaphanous-related formin 1, drf1, mdia1, p140mdia.

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: diaph1, diap1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Tetramer (from PDB file)

Resolution:

3.30Å R-factor: 0.292 R-free: 0.364

Authors:

M.Lammers,R.Rose,A.Scrima,A.Wittinghofer

Key ref:

M.Lammers et al. (2005). The regulation of mDia1 by autoinhibition and its release by Rho*GTP. Embo J, 24, 4176-4187. PubMed id: 16292343 DOI: 10.1038/sj.emboj.7600879

Date:

14-Oct-05 Release date: 07-Mar-06

Protein chains

O08808  (DIAP1_MOUSE) -  Protein diaphanous homolog 1 from Mus musculus

Seq: 1255 a.a.

Struc: 294 a.a.

Protein chains

O08808  (DIAP1_MOUSE) -  Protein diaphanous homolog 1 from Mus musculus

Seq: 1255 a.a.

Struc: 16 a.a.

DOI no: 10.1038/sj.emboj.7600879

Embo J 24:4176-4187 (2005)

PubMed id: 16292343

The regulation of mDia1 by autoinhibition and its release by Rho*GTP.

M.Lammers, R.Rose, A.Scrima, A.Wittinghofer.

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.

Selected figure(s)

Figure 5.
Figure 5 Structural model for release of DAD by Rho binding. (A) Model of a complex of mDia[N] with Rho GTP and the DCR, using the previous RhoC complex structure (Rose et al, 2005b) and the DAD complex structure obtained here and the superimposition shown in Figure 4B. (B) Details of the electrostatic repulsion between DAD and Rho in a proposed ternary mDia[N]-Rho-DAD complex; the steric clash on inserting the next DAD residue, Thr1179, is indicated by a green circle.

Figure 7.
Figure 7 Schematic two-step-binding model of DAD release from the regulatory region of mDia1 by Rho GTP, as described in the text.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Embo J (2005, 24, 4176-4187) copyright 2005.

Figures were selected by an automated process.