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PDBsum entry 1grn
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Gene regulation
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PDB id
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1grn
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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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Structures of cdc42 bound to the active and catalytically compromised forms of cdc42gap.
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Authors
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N.Nassar,
G.R.Hoffman,
D.Manor,
J.C.Clardy,
R.A.Cerione.
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Ref.
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Nat Struct Biol, 1998,
5,
1047-1052.
[DOI no: ]
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PubMed id
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Abstract
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The Rho-related small GTP-binding protein Cdc42 has a low intrinsic GTPase
activity that is significantly enhanced by its specific GTPase-activating
protein, Cdc42GAP. In this report, we present the tertiary structure for the
aluminum fluoride-promoted complex between Cdc42 and a catalytically active
domain of Cdc42GAP as well as the complex between Cdc42 and the catalytically
compromised Cdc42GAP(R305A) mutant. These structures, which mimic the transition
state for the GTP hydrolytic reaction, show the presence of an AIF3 molecule, as
was seen for the corresponding Ras-p120RasGAP complex, but in contrast to what
has been reported for the Rho-Cdc42GAP complex or for heterotrimeric G protein
alpha subunits, where AIF4- was observed. The Cdc42GAP stabilizes both the
switch I and switch II domains of Cdc42 and contributes a highly conserved
arginine (Arg 305) to the active site. Comparison of the structures for the wild
type and mutant Cdc42GAP complexes provides important insights into the
GAP-catalyzed GTP hydrolytic reaction.
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Figure 1.
Figure 1. Views of the complex between Cdc42 and the wild type
Cdc42GAP. a, A ribbon diagram of the overall complex; Cdc42
is in yellow, Cdc42GAP is in blue. The disulfide bridge is in
green. GDP, the Mg^ 2+ ion, the nucleophilic attacking water and
the AlF[3] molecule are shown in ball-and-stick representation.
The switch I and II loops of Cdc42 are highlighted. The
catalytic arginine (Arg 305) from Cdc42GAP and the highly
conserved Gln 61 from Cdc42 are also shown. b, Ribbon diagram of
the C-terminal domain of Cdc42 in complex with Cdc42GAP. This
domain is stabilized by the disulfide bridge between Cys 105 and
Cys 188 and by the hydrogen-bond interactions between the side
chains of Arg 187 and Asp 76 (represented by two dotted lines).
Figures were prepared using MOLSCRIPT^30 and Raster3D^31.
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Figure 4.
Figure 4. Stereo superposition of the Cdc42-AIF-Cdc42GAP
structure and the Gi  1-AIF[
4]^−-RGS4 complex^19. Proteins are shown in a wire
representation. Cdc42 is in yellow, Cdc42GAP is in light blue,
Gi  1
in green and RGS in gold. The GDP is shown in red (in a
ball-and-stick representation). The figure is generated by
MOLSCRIPT^30 by aligning the G domains of the two GTP-binding
proteins. RGS4 and Cdc42GAP do not have the same fold but they
contact their respective G protein targets in a similar manner.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(1998,
5,
1047-1052)
copyright 1998.
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