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PDBsum entry 1gcq
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Signaling protein/signaling protein
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PDB id
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1gcq
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Novel recognition mode between vav and grb2 sh3 domains.
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Authors
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M.Nishida,
K.Nagata,
Y.Hachimori,
M.Horiuchi,
K.Ogura,
V.Mandiyan,
J.Schlessinger,
F.Inagaki.
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Ref.
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EMBO J, 2001,
20,
2995-3007.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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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.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2001,
20,
2995-3007)
copyright 2001.
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