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PDBsum entry 1kao

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protein ligands metals links
Gtp-binding protein PDB id
1kao
Jmol
Contents
Protein chain
167 a.a. *
Ligands
GDP
Metals
_MG ×2
Waters ×70
* Residue conservation analysis
PDB id:
1kao
Name: Gtp-binding protein
Title: Crystal structure of the small g protein rap2a with gdp
Structure: Rap2a. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
1.70Å     R-factor:   0.186    
Authors: J.Cherfils,J.Menetrey,G.Le Bras
Key ref:
J.Cherfils et al. (1997). Crystal structures of the small G protein Rap2A in complex with its substrate GTP, with GDP and with GTPgammaS. EMBO J, 16, 5582-5591. PubMed id: 9312017 DOI: 10.1093/emboj/16.18.5582
Date:
01-Aug-97     Release date:   24-Dec-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P10114  (RAP2A_HUMAN) -  Ras-related protein Rap-2a
Seq:
Struc:
183 a.a.
167 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   7 terms 
  Biological process     establishment of protein localization   11 terms 
  Biochemical function     nucleotide binding     4 terms  

 

 
DOI no: 10.1093/emboj/16.18.5582 EMBO J 16:5582-5591 (1997)
PubMed id: 9312017  
 
 
Crystal structures of the small G protein Rap2A in complex with its substrate GTP, with GDP and with GTPgammaS.
J.Cherfils, J.Ménétrey, G.Le Bras, I.Janoueix-Lerosey, J.de Gunzburg, J.R.Garel, I.Auzat.
 
  ABSTRACT  
 
The small G protein Rap2A has been crystallized in complex with GDP, GTP and GTPgammaS. The Rap2A-GTP complex is the first structure of a small G protein with its natural ligand GTP. It shows that the hydroxyl group of Tyr32 forms a hydrogen bond with the gamma-phosphate of GTP and with Gly13. This interaction does not exist in the Rap2A-GTPgammaS complex. Tyr32 is conserved in many small G proteins, which probably also form this hydrogen bond with GTP. In addition, Tyr32 is structurally equivalent to a conserved arginine that binds GTP in trimeric G proteins. The actual participation of Tyr32 in GTP hydrolysis is not yet clear, but several possible roles are discussed. The conformational changes between the GDP and GTP complexes are located essentially in the switch I and II regions as described for the related oncoprotein H-Ras. However, the mobile segments vary in length and in the amplitude of movement. This suggests that even though similar regions might be involved in the GDP-GTP cycle of small G proteins, the details of the changes will be different for each G protein and will ensure the specificity of its interaction with a given set of cellular proteins.
 
  Selected figure(s)  
 
Figure 2.
Figure 2 |F[o]|-|F[c]| electron density map of Rap2A -GTP at 2.5 resolution with GTP and Tyr32 omitted from the calculation, showing that the -phosphate of GTP and the position of Tyr32 are clearly identified in the electron density.
Figure 3.
Figure 3 Interactions of Rap2A with the -phosphate of GTP.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1997, 16, 5582-5591) copyright 1997.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20649471 J.Heo (2011).
Redox control of GTPases: from molecular mechanisms to functional significance in health and disease.
  Antioxid Redox Signal, 14, 689-724.  
22081014 P.D.Mace, Y.Wallez, M.K.Dobaczewska, J.J.Lee, H.Robinson, E.B.Pasquale, and S.J.Riedl (2011).
NSP-Cas protein structures reveal a promiscuous interaction module in cell signaling.
  Nat Struct Mol Biol, 18, 1381-1387.
PDB codes: 3t6a 3t6g
20159449 H.Kawabe, A.Neeb, K.Dimova, S.M.Young, M.Takeda, S.Katsurabayashi, M.Mitkovski, O.A.Malakhova, D.E.Zhang, M.Umikawa, K.Kariya, S.Goebbels, K.A.Nave, C.Rosenmund, O.Jahn, J.Rhee, and N.Brose (2010).
Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development.
  Neuron, 65, 358-372.  
19394299 T.D.Bunney, O.Opaleye, S.M.Roe, P.Vatter, R.W.Baxendale, C.Walliser, K.L.Everett, M.B.Josephs, C.Christow, F.Rodrigues-Lima, P.Gierschik, L.H.Pearl, and M.Katan (2009).
Structural insights into formation of an active signaling complex between Rac and phospholipase C gamma 2.
  Mol Cell, 34, 223-233.
PDB codes: 2w2t 2w2v 2w2w 2w2x
18309292 A.Scrima, C.Thomas, D.Deaconescu, and A.Wittinghofer (2008).
The Rap-RapGAP complex: GTP hydrolysis without catalytic glutamine and arginine residues.
  EMBO J, 27, 1145-1153.
PDB code: 3brw
17107948 A.Splingard, J.Ménétrey, M.Perderiset, J.Cicolari, K.Regazzoni, F.Hamoudi, L.Cabanié, A.El Marjou, A.Wells, A.Houdusse, and J.de Gunzburg (2007).
Biochemical and structural characterization of the gem GTPase.
  J Biol Chem, 282, 1905-1915.
PDB code: 2cjw
17143896 D.Monleón, M.Martínez-Vicente, V.Esteve, L.Yim, S.Prado, M.E.Armengod, and B.Celda (2007).
Structural insights into the GTPase domain of Escherichia coli MnmE protein.
  Proteins, 66, 726-739.
PDB code: 1rfl
17716979 M.Miertzschke, P.Stanley, T.D.Bunney, F.Rodrigues-Lima, N.Hogg, and M.Katan (2007).
Characterization of interactions of adapter protein RAPL/Nore1B with RAP GTPases and their role in T cell migration.
  J Biol Chem, 282, 30629-30642.  
16928684 M.Kukimoto-Niino, T.Takagi, R.Akasaka, K.Murayama, T.Uchikubo-Kamo, T.Terada, M.Inoue, S.Watanabe, A.Tanaka, Y.Hayashizaki, T.Kigawa, M.Shirouzu, and S.Yokoyama (2006).
Crystal structure of the RUN domain of the RAP2-interacting protein x.
  J Biol Chem, 281, 31843-31853.
PDB codes: 2cxf 2cxl 2dwg 2dwk
15856025 A.G.Dupuy, S.L'Hoste, J.Cherfils, J.Camonis, G.Gaudriault, and J.de Gunzburg (2005).
Novel Rap1 dominant-negative mutants interfere selectively with C3G and Epac.
  Oncogene, 24, 4509-4520.  
16177825 A.Pautsch, M.Vogelsgesang, J.Tränkle, C.Herrmann, and K.Aktories (2005).
Crystal structure of the C3bot-RalA complex reveals a novel type of action of a bacterial exoenzyme.
  EMBO J, 24, 3670-3680.
PDB codes: 2a78 2a9k
15994326 M.Ye, F.Shima, S.Muraoka, J.Liao, H.Okamoto, M.Yamamoto, A.Tamura, N.Yagi, T.Ueki, and T.Kataoka (2005).
Crystal structure of M-Ras reveals a GTP-bound "off" state conformation of Ras family small GTPases.
  J Biol Chem, 280, 31267-31275.
PDB codes: 1x1r 1x1s
15728574 Y.Yu, S.Li, X.Xu, Y.Li, K.Guan, E.Arnold, and J.Ding (2005).
Structural basis for the unique biological function of small GTPase RHEB.
  J Biol Chem, 280, 17093-17100.
PDB codes: 1xtq 1xtr 1xts
14978301 C.Blouin, D.Butt, and A.J.Roger (2004).
Rapid evolution in conformational space: a study of loop regions in a ubiquitous GTP binding domain.
  Protein Sci, 13, 608-616.  
15653425 E.J.Helmreich (2004).
Structural flexibility of small GTPases. Can it explain their functional versatility?
  Biol Chem, 385, 1121-1136.  
15292263 P.P.Chakrabarti, Y.Suveyzdis, A.Wittinghofer, and K.Gerwert (2004).
Fourier transform infrared spectroscopy on the Rap.RapGAP reaction, GTPase activation without an arginine finger.
  J Biol Chem, 279, 46226-46233.  
15388940 Y.Yu, Y.Chang, S.Li, H.Hu, Q.Huang, and J.Ding (2004).
Expression, purification, crystallization and preliminary structural characterization of the GTPase domain of human Rheb.
  Acta Crystallogr D Biol Crystallogr, 60, 1883-1887.  
12682024 C.L.Tsai, and D.G.Schatz (2003).
Regulation of RAG1/RAG2-mediated transposition by GTP and the C-terminal region of RAG2.
  EMBO J, 22, 1922-1930.  
11888276 L.Renault, P.Christova, B.Guibert, S.Pasqualato, and J.Cherfils (2002).
Mechanism of domain closure of Sec7 domains and role in BFA sensitivity.
  Biochemistry, 41, 3605-3612.
PDB code: 1ku1
12084068 M.Stumber, C.Herrmann, S.Wohlgemuth, H.R.Kalbitzer, W.Jahn, and M.Geyer (2002).
Synthesis, characterization and application of two nucleoside triphosphate analogues, GTPgammaNH(2) and GTPgammaF.
  Eur J Biochem, 269, 3270-3278.  
11812780 T.Brinkmann, O.Daumke, U.Herbrand, D.Kühlmann, P.Stege, M.R.Ahmadian, and A.Wittinghofer (2002).
Rap-specific GTPase activating protein follows an alternative mechanism.
  J Biol Chem, 277, 12525-12531.  
11566135 S.Padmanabhan, and D.M.Freymann (2001).
The conformation of bound GMPPNP suggests a mechanism for gating the active site of the SRP GTPase.
  Structure, 9, 859-867.
PDB codes: 1jpj 1jpn
11266366 S.Pasqualato, J.Ménétrey, M.Franco, and J.Cherfils (2001).
The structural GDP/GTP cycle of human Arf6.
  EMBO Rep, 2, 234-238.
PDB codes: 1hfv 2j5x
10657303 C.Fenwick, S.Y.Na, R.E.Voll, H.Zhong, S.Y.Im, J.W.Lee, and S.Ghosh (2000).
A subclass of Ras proteins that regulate the degradation of IkappaB.
  Science, 287, 869-873.  
10944341 D.Chattopadhyay, C.D.Smith, J.Barchue, and G.Langsley (2000).
Plasmodium falciparum rab6 GTPase: expression, purification, crystallization and preliminary crystallographic studies.
  Acta Crystallogr D Biol Crystallogr, 56, 1017-1019.  
10574788 A.J.Scheidig, C.Burmester, and R.S.Goody (1999).
The pre-hydrolysis state of p21(ras) in complex with GTP: new insights into the role of water molecules in the GTP hydrolysis reaction of ras-like proteins.
  Structure, 7, 1311-1324.
PDB codes: 1ctq 1qra
10431174 J.Cherfils, and P.Chardin (1999).
GEFs: structural basis for their activation of small GTP-binding proteins.
  Trends Biochem Sci, 24, 306-311.  
10591105 J.Ménétrey, and J.Cherfils (1999).
Structure of the small G protein Rap2 in a non-catalytic complex with GTP.
  Proteins, 37, 465-473.
PDB code: 3rap
  10211824 M.G.Rudolph, A.Wittinghofer, and I.R.Vetter (1999).
Nucleotide binding to the G12V-mutant of Cdc42 investigated by X-ray diffraction and fluorescence spectroscopy: two different nucleotide states in one crystal.
  Protein Sci, 8, 778-787.
PDB code: 1a4r
10469145 P.Meyer, J.Janin, and S.Baudet-Nessler (1999).
p55-hGRF, a short natural form of the Ras-GDP exchange factor high yield production and characterization.
  Eur J Biochem, 263, 806-816.  
10085114 V.Nancy, R.M.Wolthuis, M.F.de Tand, I.Janoueix-Lerosey, J.L.Bos, and J.de Gunzburg (1999).
Identification and characterization of potential effector molecules of the Ras-related GTPase Rap2.
  J Biol Chem, 274, 8737-8745.  
9772163 D.E.Coleman, and S.R.Sprang (1998).
Crystal structures of the G protein Gi alpha 1 complexed with GDP and Mg2+: a crystallographic titration experiment.
  Biochemistry, 37, 14376-14385.
PDB code: 1bof
9622490 J.Van Dijk, C.Fernandez, and P.Chaussepied (1998).
Effect of ATP analogues on the actin-myosin interface.
  Biochemistry, 37, 8385-8394.  
9545299 K.Ihara, S.Muraguchi, M.Kato, T.Shimizu, M.Shirakawa, S.Kuroda, K.Kaibuchi, and T.Hakoshima (1998).
Crystal structure of human RhoA in a dominantly active form complexed with a GTP analogue.
  J Biol Chem, 273, 9656-9666.
PDB code: 1a2b
9631293 S.J.Gamblin, and S.J.Smerdon (1998).
GTPase-activating proteins and their complexes.
  Curr Opin Struct Biol, 8, 195-201.  
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.  
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 codes are shown on the right.