PDBsum entry 1v9d

Protein binding

PDB id: 1v9d

Contents

Protein chains

308 a.a. *

321 a.a. *

278 a.a. *

Ligands

SO4 ×3

Waters ×192

* Residue conservation analysis

PDB id:

1v9d

Name:

Protein binding

Title:

Crystal structure of the core fh2 domain of mouse mdia1

Structure:

Diaphanous protein homolog 1. Chain: a, b, c, d. Fragment: core fh2 domain. Synonym: diaphanous-related formin 1, drf1, mdia1, p140mdia. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Tetramer (from PQS)

Resolution:

2.60Å R-factor: 0.236 R-free: 0.267

Authors:

A.Shimada,M.Nyitrai,I.R.Vetter,D.Kuhlmann,B.Bugyi,S.Narumiya, M.A.Geeves,A.Wittinghofer

Key ref:

A.Shimada et al. (2004). The core FH2 domain of diaphanous-related formins is an elongated actin binding protein that inhibits polymerization. Mol Cell, 13, 511-522. PubMed id: 14992721 DOI: 10.1016/S1097-2765(04)00059-0

Date:

24-Jan-04 Release date: 09-Mar-04

Protein chains

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

Seq: 1255 a.a.

Struc: 308 a.a.

Protein chain

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

Seq: 1255 a.a.

Struc: 321 a.a.

Protein chain

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

Seq: 1255 a.a.

Struc: 278 a.a.

DOI no: 10.1016/S1097-2765(04)00059-0

Mol Cell 13:511-522 (2004)

PubMed id: 14992721

The core FH2 domain of diaphanous-related formins is an elongated actin binding protein that inhibits polymerization.

A.Shimada, M.Nyitrai, I.R.Vetter, D.Kühlmann, B.Bugyi, S.Narumiya, M.A.Geeves, A.Wittinghofer.

ABSTRACT

Diaphanous-related formins (Drf) are activated by Rho GTP binding proteins and induce polymerization of unbranched actin filaments. They contain three formin homology domains. Evidence as to the effect of formins on actin polymerization were obtained using FH2/FH1 constructs of various length from different Drfs. Here we define the core FH2 domain as a proteolytically stable domain of approximately 338 residues. The monomeric FH2 domains from mDia1 and mDia3 inhibit polymerization of actin and can bind in a 1:1 complex with F-actin at micromolar concentrations. The X-ray structure analysis of the domain shows an elongated, crescent-shaped molecule consisting of three helical subdomains. The most highly conserved regions of the domain span a distance of 75 A and are both required for barbed-end inhibition. A construct containing an additional 72 residue linker has dramatically different properties: It oligomerizes and induces actin polymerization at subnanomolar concentration.

Selected figure(s)

Figure 3.
Figure 3. X-Ray Structure Solution of the Core FH2 Domain from mDia1(A) Stereo view of the asymmetric unit. Molecules A, B, C, and D of the asymmetric unit are colored red, green, blue, and yellow, respectively, with NH[2] and COOH termini labeled correspondingly.(B) A representative stereo electron density map. An 2F[o] − F[c] electron density map, contoured at 1.2σ, of the interface between α13 and surrounding helices α9 and 3^10. The residues involved in the interaction are labeled.

Figure 4.
Figure 4. Structural Analysis of the mDia1 Core FH2 Domain(A) Ribbon diagram of the core FH2 domain. The NH[2]-terminal, three-helix-bundle, and FH2 motif subdomains are colored red, blue, and green, respectively. The region corresponding to the highly conserved ^967GNXMN^971 motif is colored purple. The NH[2] and COOH termini of the molecule are indicated by N and C, respectively. Secondary structures are numbered consecutively. Ile845, Met970, Lys989, Lys994, Lys999, Arg919, and Asp1067 are shown as ball-and-stick representation. Distance between Ile845 and Met970 and approximate locations of the FH1 domain, linker, and DAD in mDia1 are indicated.(B) A buried salt bridge. A salt bridge between Arg919 and Asp1067 is shown as ball-and-stick representation together with surrounding hydrophobic residues, as indicated.(C) Superimposition of the four molecules in the asymmetric unit. Molecules A, B, C, and D, colored in red, green, blue, and yellow, respectively, were superimposed on the three-helix-bundle subdomains, and are oriented as in (A). Note that the FH2 subdomain exhibited the highest conformational differences.(D) Conserved residues. Surface representation of the mDia1-FH2 core domain with residues conserved in the six formin family proteins colored orange and those conserved in five of six colored yellow. Residues mentioned in the text are indicated. Left and right: orientation as in Figure 3B and rotated 180°, respectively.

The above figures are reprinted by permission from Cell Press: Mol Cell (2004, 13, 511-522) copyright 2004.

Figures were selected by an automated process.