PDBsum entry 1gcp

Signaling protein

PDB id: 1gcp

Contents

Protein chains

65 a.a. *

67 a.a. *

Waters ×190

* Residue conservation analysis

PDB id:

1gcp

Name:

Signaling protein

Title:

Crystal structure of vav sh3 domain

Structure:

Vav proto-oncogene. Chain: a, b, c, d. Fragment: n-terminal domain. Engineered: yes

Source:

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

Resolution:

2.10Å R-factor: 0.193 R-free: 0.253

Authors:

M.Nishida,K.Nagata,Y.Hachimori,K.Ogura,F.Inagaki

Key ref:

M.Nishida et al. (2001). Novel recognition mode between Vav and Grb2 SH3 domains. EMBO J, 20, 2995-3007. PubMed id: 11406576 DOI: 10.1093/emboj/20.12.2995

Date:

08-Aug-00 Release date: 08-Aug-01

Protein chain

P27870  (VAV_MOUSE) -  Proto-oncogene vav from Mus musculus

Seq: 845 a.a.

Struc: 65 a.a.

Protein chains

P27870  (VAV_MOUSE) -  Proto-oncogene vav from Mus musculus

Seq: 845 a.a.

Struc: 67 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: Chains A, B, C, D: E.C.?

DOI no: 10.1093/emboj/20.12.2995

EMBO J 20:2995-3007 (2001)

PubMed id: 11406576

Novel recognition mode between Vav and Grb2 SH3 domains.

M.Nishida, K.Nagata, Y.Hachimori, M.Horiuchi, K.Ogura, V.Mandiyan, J.Schlessinger, F.Inagaki.

ABSTRACT

Vav is a guanine nucleotide exchange factor for the Rho/Rac family that is expressed exclusively in hematopoietic cells. Growth factor receptor-bound protein 2 (Grb2) has been proposed to play important roles in the membrane localization and activation of Vav through dimerization of its C-terminal Src-homology 3 (SH3) domain (GrbS) and the N-terminal SH3 domain of Vav (VavS). The crystal structure of VavS complexed with GrbS has been solved. VavS is distinct from other SH3 domain proteins in that its binding site for proline-rich peptides is blocked by its own RT loop. One of the ends of the VavS beta-barrel forms a concave hydrophobic surface. The GrbS components make a contiguous complementary interface with the VavS surface. The binding site of GrbS for VavS partially overlaps with the canonical binding site for proline-rich peptides, but is definitely different. Mutations at the interface caused a decrease in the binding affinity of VavS for GrbS by 4- to 40-fold. The structure reveals how GrbS discriminates VavS specifically from other signaling molecules without binding to the proline-rich motif.

Selected figure(s)

Figure 3.
Figure 3 Tetraproline region and PPII helix-binding site of VavS. (A) The ribbon diagram for VavS in the complex crystal is shown with the tetraproline region close to the viewer. Residues 606 -612 encompassing the tetraproline region, and the residues interacting with them or expected to form the PPII helix-binding site are drawn as rods in red and blue, respectively. (B) The molecular surface of VavS by GRASP (Nicholls et al., 1991) is colored according to the local electrostatic potential, with colors ranging from blue (positive) to red (negative) through white (neutral). The tetraproline region is drawn as red rods, and the peptide ligand for the Sem-5 SH3 domain is superposed on the molecular surface (yellow rods). The expected binding sites of VavS for the proline-rich peptide are labeled with their identification codes.

Figure 5.
Figure 5 Schematic views of the VavS -GrbS A interface. (A) The molecular surface of VavS is shown as a transparent worm with the VavS -GrbSA interface close to the viewer. The VavS residues at the interface are drawn as green rods. For clarity, some residues that interact minimally with GrbS A are omitted (His634, Cys652, Val655 and His 656). The polypeptide backbone of the N-terminal tail derived from the expression vector is traced as a dotted line in white. (B) The side chains (rods) and polypeptide backbone (magenta tubes) of the GrbS residues at the interface are superposed on VavS. (C) The molecular surfaces of the Abl (left) (Musacchio et al., 1994) and Hck (right) (Sicheri et al., 1997) SH3 domains are shown in the same orientation as that of VavS in (A) and (B). Only the regions corresponding to residues 595 -659 of VavS are shown.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2001, 20, 2995-3007) copyright 2001.

Figures were selected by an automated process.