1X1R

Crystal structure of M-Ras in complex with GDP


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.30 Å
  • R-Value Free: 0.200 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.183 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Crystal Structure of M-Ras Reveals a GTP-bound "Off" State Conformation of Ras Family Small GTPases

Ye, M.Shima, F.Muraoka, S.Liao, J.Okamoto, H.Yamamoto, M.Tamura, A.Yagi, N.Ueki, T.Kataoka, T.

(2005) J Biol Chem 280: 31267-31275

  • DOI: https://doi.org/10.1074/jbc.M505503200
  • Primary Citation of Related Structures:  
    1X1R, 1X1S

  • PubMed 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.


  • Organizational Affiliation

    Division of Molecular Biology, Department of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Ras-related protein M-Ras178Mus musculusMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for O08989 (Mus musculus)
Explore O08989 
Go to UniProtKB:  O08989
IMPC:  MGI:1100856
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO08989
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GDP
Query on GDP

Download Ideal Coordinates CCD File 
C [auth A]GUANOSINE-5'-DIPHOSPHATE
C10 H15 N5 O11 P2
QGWNDRXFNXRZMB-UUOKFMHZSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
B [auth A]MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.30 Å
  • R-Value Free: 0.200 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.183 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 64.899α = 90
b = 70.668β = 90
c = 43.422γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
CCP4data scaling
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-07-26
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-10-25
    Changes: Data collection, Database references, Derived calculations, Refinement description