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G-protein PDB id
1rgp
Jmol
Contents
Protein chain
189 a.a. *
Waters ×261
* Residue conservation analysis
PDB id:
1rgp
Name: G-protein
Title: Gtpase-activation domain from rhogap
Structure: Rhogap. Chain: a. Fragment: gtpase activation domain. Synonym: cdc42 gtpase-activating protein. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: cytoplasm. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.00Å     R-factor:   0.220     R-free:   0.283
Authors: T.Barrett,B.Xiao,E.J.Dodson,G.Dodson,S.B.Ludbrook, K.Nurmahomed,S.J.Gamblin,A.Musacchio,S.J.Smerdon, J.F.Eccleston
Key ref: T.Barrett et al. (1997). The structure of the GTPase-activating domain from p50rhoGAP. Nature, 385, 458-461. PubMed id: 9009196 DOI: 10.1038/385458a0
Date:
05-Dec-96     Release date:   15-Oct-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q07960  (RHG01_HUMAN) -  Rho GTPase-activating protein 1
Seq:
Struc: 		439 a.a.
189 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   1 term 
  Biological process     signal transduction   1 term 

 

 
DOI no: 10.1038/385458a0 Nature 385:458-461 (1997)
PubMed id: 9009196  
 
 
The structure of the GTPase-activating domain from p50rhoGAP.
T.Barrett, B.Xiao, E.J.Dodson, G.Dodson, S.B.Ludbrook, K.Nurmahomed, S.J.Gamblin, A.Musacchio, S.J.Smerdon, J.F.Eccleston.
 
  ABSTRACT  
 
Members of the Rho family of small G proteins transduce signals from plasma-membrane receptors and control cell adhesion, motility and shape by actin cytoskeleton formation. They also activate other kinase cascades. Like all other GTPases, Rho proteins act as molecular switches, with an active GTP-bound form and an inactive GDP-bound form. The active conformation is promoted by guanine-nucleotide exchange factors, and the inactive state by GTPase-activating proteins (GAPs) which stimulate the intrinsic GTPase activity of small G proteins. Rho-specific GAP domains are found in a wide variety of large, multi-functional proteins. Here we report the crystal structure of an active 242-residue C-terminal fragment of human p50rhoGAP. The structure is an unusual arrangement of nine alpha-helices, the core of which includes a four-helix bundle. Residues conserved across the rhoGAP family are largely confined to one face of this bundle, which may be an interaction site for target G proteins. In particular, we propose that Arg 85 and Asn 194 are involved in binding G proteins and enhancing GTPase activity.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21170032 L.J.Neukomm, A.P.Frei, J.Cabello, J.M.Kinchen, R.Zaidel-Bar, Z.Ma, L.B.Haney, J.Hardin, K.S.Ravichandran, S.Moreno, and M.O.Hengartner (2011).
Loss of the RhoGAP SRGP-1 promotes the clearance of dead and injured cells in Caenorhabditis elegans.
  Nat Cell Biol, 13, 79-86.  
20660160 Y.T.Zhou, L.L.Chew, S.C.Lin, and B.C.Low (2010).
The BNIP-2 and Cdc42GAP homology (BCH) domain of p50RhoGAP/Cdc42GAP sequesters RhoA from inactivation by the adjacent GTPase-activating protein domain.
  Mol Biol Cell, 21, 3232-3246.  
18929667 F.Jelen, P.Lachowicz, W.Apostoluk, A.Mateja, Z.S.Derewenda, and J.Otlewski (2009).
Dissecting the thermodynamics of GAP-RhoA interactions.
  J Struct Biol, 165, 10-18.  
19321438 V.B.Kurella, J.M.Richard, C.L.Parke, L.F.Lecour, H.D.Bellamy, and D.K.Worthylake (2009).
Crystal Structure of the GTPase-activating Protein-related Domain from IQGAP1.
  J Biol Chem, 284, 14857-14865.
PDB code: 3fay
16380373 G.Sirokmány, L.Szidonya, K.Káldi, Z.Gáborik, E.Ligeti, and M.Geiszt (2006).
Sec14 homology domain targets p50RhoGAP to endosomes and provides a link between Rab and Rho GTPases.
  J Biol Chem, 281, 6096-6105.  
16777849 H.Liu, T.Nakazawa, T.Tezuka, and T.Yamamoto (2006).
Physical and functional interaction of Fyn tyrosine kinase with a brain-enriched Rho GTPase-activating protein TCGAP.
  J Biol Chem, 281, 23611-23619.  
15611138 I.Lavelin, and B.Geiger (2005).
Characterization of a novel GTPase-activating protein associated with focal adhesions and the actin cytoskeleton.
  J Biol Chem, 280, 7178-7185.  
15596440 P.Moskwa, M.H.Paclet, M.C.Dagher, and E.Ligeti (2005).
Autoinhibition of p50 Rho GTPase-activating protein (GAP) is released by prenylated small GTPases.
  J Biol Chem, 280, 6716-6720.  
15507211 B.Canagarajah, F.C.Leskow, J.Y.Ho, H.Mischak, L.F.Saidi, M.G.Kazanietz, and J.H.Hurley (2004).
Structural mechanism for lipid activation of the Rac-specific GAP, beta2-chimaerin.
  Cell, 119, 407-418.
PDB code: 1xa6
15282546 J.M.Mingot, M.T.Bohnsack, U.Jäkle, and D.Görlich (2004).
Exportin 7 defines a novel general nuclear export pathway.
  EMBO J, 23, 3227-3236.  
15292224 J.Sun, and J.T.Barbieri (2004).
ExoS Rho GTPase-activating protein activity stimulates reorganization of the actin cytoskeleton through Rho GTPase guanine nucleotide disassociation inhibitor.
  J Biol Chem, 279, 42936-42944.  
15249689 V.A.Podolskiy, E.Narimanov, W.Fang, and H.Cao (2004).
Chaotic microlasers based on dynamical localization.
  Proc Natl Acad Sci U S A, 101, 10498-10500.  
15302923 Z.J.Su, C.N.Hahn, G.J.Goodall, N.M.Reck, A.F.Leske, A.Davy, G.Kremmidiotis, M.A.Vadas, and J.R.Gamble (2004).
A vascular cell-restricted RhoGAP, p73RhoGAP, is a key regulator of angiogenesis.
  Proc Natl Acad Sci U S A, 101, 12212-12217.  
12788707 A.T.Mintie, R.S.Heichen, K.Cromack, D.D.Myrold, and P.J.Bottomley (2003).
Ammonia-oxidizing bacteria along meadow-to-forest transects in the Oregon Cascade Mountains.
  Appl Environ Microbiol, 69, 3129-3136.  
12857875 T.Nakazawa, A.M.Watabe, T.Tezuka, Y.Yoshida, K.Yokoyama, H.Umemori, A.Inoue, S.Okabe, T.Manabe, and T.Yamamoto (2003).
p250GAP, a novel brain-enriched GTPase-activating protein for Rho family GTPases, is involved in the N-methyl-d-aspartate receptor signaling.
  Mol Biol Cell, 14, 2921-2934.  
12531901 T.Okabe, T.Nakamura, Y.N.Nishimura, K.Kohu, S.Ohwada, Y.Morishita, and T.Akiyama (2003).
RICS, a novel GTPase-activating protein for Cdc42 and Rac1, is involved in the beta-catenin-N-cadherin and N-methyl-D-aspartate receptor signaling.
  J Biol Chem, 278, 9920-9927.  
12145202 A.R.Marquitz, J.C.Harrison, I.Bose, T.R.Zyla, J.N.McMillan, and D.J.Lew (2002).
The Rho-GAP Bem2p plays a GAP-independent role in the morphogenesis checkpoint.
  EMBO J, 21, 4012-4025.  
  11754636 K.A.Vallis, Z.Chen, W.L.Stanford, M.Yu, R.P.Hill, and A.Bernstein (2002).
Identification of radiation-responsive genes in vitro using a gene trap strategy predicts for modulation of expression by radiation in vivo.
  Radiat Res, 157, 8.  
  11854031 Z.Zhang, C.Wu, S.Wang, W.Huang, Z.Zhou, K.Ying, Y.Xie, and Y.Mao (2002).
Cloning and characterization of ARHGAP12, a novel human rhoGAP gene.
  Int J Biochem Cell Biol, 34, 325-331.  
11238453 X.R.Ren, Q.S.Du, Y.Z.Huang, S.Z.Ao, L.Mei, and W.C.Xiong (2001).
Regulation of CDC42 GTPase by proline-rich tyrosine kinase 2 interacting with PSGAP, a novel pleckstrin homology and Src homology 3 domain containing rhoGAP protein.
  J Cell Biol, 152, 971-984.  
10799524 B.C.Low, K.T.Seow, and G.R.Guy (2000).
Evidence for a novel Cdc42GAP domain at the carboxyl terminus of BNIP-2.
  J Biol Chem, 275, 14415-14422.  
11163217 C.E.Stebbins, and J.E.Galán (2000).
Modulation of host signaling by a bacterial mimic: structure of the Salmonella effector SptP bound to Rac1.
  Mol Cell, 6, 1449-1460.
PDB codes: 1g4u 1g4w
10489445 K.Longenecker, P.Read, U.Derewenda, Z.Dauter, X.Liu, S.Garrard, L.Walker, A.V.Somlyo, R.K.Nakamoto, A.P.Somlyo, and Z.S.Derewenda (1999).
How RhoGDI binds Rho.
  Acta Crystallogr D Biol Crystallogr, 55, 1503-1515.
PDB code: 1cc0
10364218 M.Sekimata, Y.Kabuyama, Y.Emori, and Y.Homma (1999).
Morphological changes and detachment of adherent cells induced by p122, a GTPase-activating protein for Rho.
  J Biol Chem, 274, 17757-17762.  
10232922 P.J.Sheffield, U.Derewenda, J.Taylor, T.J.Parsons, and Z.S.Derewenda (1999).
Expression, purification and crystallization of a BH domain from the GTPase regulatory protein associated with focal adhesion kinase.
  Acta Crystallogr D Biol Crystallogr, 55, 356-359.  
10394366 R.C.Hillig, L.Renault, I.R.Vetter, T.Drell, A.Wittinghofer, and J.Becker (1999).
The crystal structure of rna1p: a new fold for a GTPase-activating protein.
  Mol Cell, 3, 781-791.
PDB code: 1yrg
10601011 V.Mandiyan, J.Andreev, J.Schlessinger, and S.R.Hubbard (1999).
Crystal structure of the ARF-GAP domain and ankyrin repeats of PYK2-associated protein beta.
  EMBO J, 18, 6890-6898.
PDB code: 1dcq
9535855 B.Zhang, J.Chernoff, and Y.Zheng (1998).
Interaction of Rac1 with GTPase-activating proteins and putative effectors. A comparison with Cdc42 and RhoA.
  J Biol Chem, 273, 8776-8782.  
9548756 B.Zhang, and Y.Zheng (1998).
Regulation of RhoA GTP hydrolysis by the GTPase-activating proteins p190, p50RhoGAP, Bcr, and 3BP-1.
  Biochemistry, 37, 5249-5257.  
9759495 D.A.Fruman, R.E.Meyers, and L.C.Cantley (1998).
Phosphoinositide kinases.
  Annu Rev Biochem, 67, 481-507.  
9632678 D.A.Leonard, R.Lin, R.A.Cerione, and D.Manor (1998).
Biochemical studies of the mechanism of action of the Cdc42-GTPase-activating protein.
  J Biol Chem, 273, 16210-16215.  
9546212 E.F.Pai (1998).
The alpha and beta of turning on a molecular switch.
  Nat Struct Biol, 5, 259-263.  
9697416 K.Scheffzek, M.R.Ahmadian, and A.Wittinghofer (1998).
GTPase-activating proteins: helping hands to complement an active site.
  Trends Biochem Sci, 23, 257-262.  
9852136 N.Tatsis, D.A.Lannigan, and I.G.Macara (1998).
The function of the p190 Rho GTPase-activating protein is controlled by its N-terminal GTP binding domain.
  J Biol Chem, 273, 34631-34638.  
9446556 N.Vitale, J.Moss, and M.Vaughan (1998).
Molecular characterization of the GTPase-activating domain of ADP-ribosylation factor domain protein 1 (ARD1).
  J Biol Chem, 273, 2553-2560.  
9631293 S.J.Gamblin, and S.J.Smerdon (1998).
GTPase-activating proteins and their complexes.
  Curr Opin Struct Biol, 8, 195-201.  
9268338 B.Zhang, Z.X.Wang, and Y.Zheng (1997).
Characterization of the interactions between the small GTPase Cdc42 and its GTPase-activating proteins and putative effectors. Comparison of kinetic properties of Cdc42 binding to the Cdc42-interactive domains.
  J Biol Chem, 272, 21999-22007.  
9434896 M.Geyer, and A.Wittinghofer (1997).
GEFs, GAPs, GDIs and effectors: taking a closer (3D) look at the regulation of Ras-related GTP-binding proteins.
  Curr Opin Struct Biol, 7, 786-792.  
9407060 R.Li, B.Zhang, and Y.Zheng (1997).
Structural determinants required for the interaction between Rho GTPase and the GTPase-activating domain of p190.
  J Biol Chem, 272, 32830-32835.  
  9348541 R.T.Müller, U.Honnert, J.Reinhard, and M.Bähler (1997).
The rat myosin myr 5 is a GTPase-activating protein for Rho in vivo: essential role of arginine 1695.
  Mol Biol Cell, 8, 2039-2053.  
9434906 S.R.Sprang (1997).
G proteins, effectors and GAPs: structure and mechanism.
  Curr Opin Struct Biol, 7, 849-856.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.