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PDBsum entry 1x1r

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protein ligands metals links
Signaling protein PDB id
1x1r
Jmol
Contents
Protein chain
169 a.a. *
Ligands
GDP
Metals
_MG
Waters ×238
* Residue conservation analysis
PDB id:
1x1r
Name: Signaling protein
Title: Crystal structure of m-ras in complex with gdp
Structure: Ras-related protein m-ras. Chain: a. Fragment: residues 1-178. Synonym: ras-related protein r-ras3, muscle and microspikes ras, x-ras, gtpase. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.30Å     R-factor:   0.183     R-free:   0.200
Authors: M.Ye,F.Shima,S.Muraoka,J.Liao,H.Okamoto,M.Yamamoto,A.Tamura, N.Yagi,T.Ueki,T.Kataoka
Key ref:
M.Ye et al. (2005). Crystal structure of M-Ras reveals a GTP-bound "off" state conformation of Ras family small GTPases. J Biol Chem, 280, 31267-31275. PubMed id: 15994326 DOI: 10.1074/jbc.M505503200
Date:
12-Apr-05     Release date:   26-Jul-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O08989  (RASM_MOUSE) -  Ras-related protein M-Ras
Seq:
Struc:
208 a.a.
169 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     signal transduction   3 terms 
  Biochemical function     GTP binding     1 term  

 

 
DOI no: 10.1074/jbc.M505503200 J Biol Chem 280:31267-31275 (2005)
PubMed id: 15994326  
 
 
Crystal structure of M-Ras reveals a GTP-bound "off" state conformation of Ras family small GTPases.
M.Ye, F.Shima, S.Muraoka, J.Liao, H.Okamoto, M.Yamamoto, A.Tamura, N.Yagi, T.Ueki, T.Kataoka.
 
  ABSTRACT  
 
Although some members of Ras family small GTPases, including M-Ras, share the primary structure of their effector regions with Ras, they exhibit vastly different binding properties to Ras effectors such as c-Raf-1. We have solved the crystal structure of M-Ras in the GDP-bound and guanosine 5'-(beta,gamma-imido)triphosphate (Gpp(NH)p)-bound forms. The overall structure of M-Ras resembles those of H-Ras and Rap2A, except that M-Ras-Gpp(NH)p exhibits a distinctive switch I conformation, which is caused by impaired intramolecular interactions between Thr-45 (corresponding to Thr-35 of H-Ras) of the effector region and the gamma-phosphate of Gpp(NH)p. Previous 31P NMR studies showed that H-Ras-Gpp(NH)p exists in two interconverting conformations, states 1 and 2. Whereas state 2 is a predominant form of H-Ras and corresponds to the "on" conformation found in the complex with effectors, state 1 is thought to represent the "off" conformation, whose tertiary structure remains unknown. 31P NMR analysis shows that free M-Ras-Gpp(NH)p predominantly assumes the state 1 conformation, which undergoes conformational transition to state 2 upon association with c-Raf-1. These results indicate that the solved structure of M-Ras-Gp-p(NH)p corresponds to the state 1 conformation. The predominance of state 1 in M-Ras is likely to account for its weak binding ability to the Ras effectors, suggesting the importance of the tertiary structure factor in small GTPase-effector interaction. Further, the first determination of the state 1 structure provides a molecular basis for developing novel anti-cancer drugs as compounds that hold Ras in the state 1 "off" conformation.
 
  Selected figure(s)  
 
Figure 3.
FIG. 3. Comparison of the Mg2+-binding sites between M-Ras and H-Ras in the Gpp(NH)p-bound forms. A, schematic drawing of the Mg2+-binding site showing the ligands of the first coordination sphere of Mg2+ ion and some of the interactions of these ligands. Wat, a water molecule. B, direct and Mg2+-coordinated indirect interactions among Thr-45, Ser-27, Asp-67, and the -phosphate of M-Ras and interactions among Thr-35, Ser-27, Asp-57, and -phosphate of H-Ras are highlighted. Nucleotide and the side chains of the residues are shown in the ball-and-stick model. The Mg2+ ion is shown in yellow. Colors for the atoms of Gpp(NH)p are identical to those used in Fig. 1B. This figure was generated with Raster3D (24) and MOLSCRIPT (25).
Figure 7.
FIG. 7. Comparison of the switch I surface groove between M-Ras-Gp-p(NH)p and H-Ras-Gpp(NH)p. The surface groove formed around the -phosphate of M-Ras is highlighted by a red arrow. The switch I and switch II residues are shown in yellow and green, respectively. Gpp(NH)p is shown by a CPK model. A part of switch II of M-Ras, corresponding to residues 69-73, is missing. The image was prepared by using the program PyMOL (DeLano Scientific).
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 31267-31275) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20696399 R.B.Fenwick, L.J.Campbell, K.Rajasekar, S.Prasannan, D.Nietlispach, J.Camonis, D.Owen, and H.R.Mott (2010).
The RalB-RLIP76 complex reveals a novel mode of ral-effector interaction.
  Structure, 18, 985-995.
PDB codes: 2kwh 2kwi
19265520 A.F.Neuwald (2009).
The glycine brace: a component of Rab, Rho, and Ran GTPases associated with hinge regions of guanine- and phosphate-binding loops.
  BMC Struct Biol, 9, 11.  
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
18386081 J.Petersen, C.J.Mitchell, K.Fisher, and D.J.Lowe (2008).
Structural basis for VO(2+)-inhibition of nitrogenase activity: (B) pH-sensitive inner-sphere rearrangements in the 1H-environment of the metal coordination site of the nitrogenase Fe-protein identified by ENDOR spectroscopy.
  J Biol Inorg Chem, 13, 637-650.  
17996962 K.Yokoyama, J.R.Gillespie, W.C.Van Voorhis, F.S.Buckner, and M.H.Gelb (2008).
Protein geranylgeranyltransferase-I of Trypanosoma cruzi.
  Mol Biochem Parasitol, 157, 32-43.  
18940599 M.B.Hamaneh, and M.Buck (2008).
Tripping a switch: PDZRhoGEF rgRGS-bound Galpha13.
  Structure, 16, 1439-1441.  
18348980 M.J.Phillips, G.Calero, B.Chan, S.Ramachandran, and R.A.Cerione (2008).
Effector proteins exert an important influence on the signaling-active state of the small GTPase Cdc42.
  J Biol Chem, 283, 14153-14164.
PDB code: 2qrz
17385754 C.Kötting, A.Kallenbach, Y.Suveyzdis, C.Eichholz, and K.Gerwert (2007).
Surface change of Ras enabling effector binding monitored in real time at atomic resolution.
  Chembiochem, 8, 781-787.  
17302736 M.Spoerner, A.Nuehs, C.Herrmann, G.Steiner, and H.R.Kalbitzer (2007).
Slow conformational dynamics of the guanine nucleotide-binding protein Ras complexed with the GTP analogue GTPgammaS.
  FEBS J, 274, 1419-1433.  
16980617 N.Nuñez Rodriguez, I.N.Lee, A.Banno, H.F.Qiao, R.F.Qiao, Z.Yao, T.Hoang, A.C.Kimmelman, and A.M.Chan (2006).
Characterization of R-ras3/m-ras null mice reveals a potential role in trophic factor signaling.
  Mol Cell Biol, 26, 7145-7154.  
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.