PDBsum entry: 1grn

Gene regulation

PDB-id: 1grn

Biological unit* = asymmetric unit, as shown
(*as deduced by PQS)

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Description

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References

PROCHECK

Protein chains

191 a.a. *

197 a.a. *

Ligands

GDP-AF3

Metal ions

_MG

Waters ×72

* Residue conservation analysis

Tools

Clefts Calculation

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PDB id:

1grn

Name:

Gene regulation

Title:

Crystal structure of the cdc42/cdc42gap/alf3 complex.

Structure:

Protein (gtp binding protein). Chain: a. Fragment: cdc42. Engineered: yes. Other_details: gdp, mg++, alf3. Protein (rho gtpase activating protein). Chain: b. Fragment: c-terminal domain of cdc42gap. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: cytoplasm. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: proteins expressed in escherichia coli as his-tagged fusion proteins.. His-tagged fusion proteins.

Biological unit:

Dimer (from PQS)

UniProt:

Chain A: P60953 (CDC42_HUMAN)

Seq:	191 a.a.
Struc:	191 a.a.*

Chain B: Q07960 (RHG01_HUMAN)

Seq:

Struc:

Seq:

439 a.a.

Struc:

197 a.a.

Key:	PfamA domain
Secondary structure	CATH domain

* PDB and UniProt seqs differ at 9 residue positions (black crosses)

Resolution:

2.10Å

R-factor:

0.211

R-free:

0.259

Authors:

N.Nassar,G.R.Hoffman,J.C.Clardy,R.A.Cerione

Key ref:

N.Nassar et al. (1998). Structures of Cdc42 bound to the active and catalytically compromised forms of Cdc42GAP.. Nat Struct Biol, 5, 1047-1052. [PubMed id: 9846874] [DOI: 10.1038/4156]

Date:

30-Jul-98

Release date:

22-Dec-99

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Clefts

Surface

Key reference

DOI no: 10.1038/4156

Nat Struct Biol 5:1047-1052 (1998)

PubMed id: 9846874

Structures of Cdc42 bound to the active and catalytically compromised forms of Cdc42GAP.

N.Nassar, G.R.Hoffman, D.Manor, J.C.Clardy, R.A.Cerione.

ABSTRACT

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.

Selected figure(s)

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.

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.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (1998, 5, 1047-1052) copyright 1998.

Figures were selected by an automated process.