8BWG

HRas (1-166) Y64 phosphorylation


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.32 Å
  • R-Value Free: 0.174 
  • R-Value Work: 0.135 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Far-reaching effects of tyrosine64 phosphorylation on Ras revealed with BeF 3 - complexes.

Baumann, P.Jin, Y.

(2024) Commun Chem 7: 19-19

  • DOI: https://doi.org/10.1038/s42004-024-01105-6
  • Primary Citation of Related Structures:  
    8BWG, 8CNJ, 8CNN

  • PubMed Abstract: 

    Tyrosine phosphorylation on Ras by Src kinase is known to uncouple Ras from upstream regulation and downstream communication. However, the mechanisms by which phosphorylation modulates these interactions have not been detailed. Here, the major mono-phosphorylation level on tyrosine64 is quantified by 31 P NMR and mutagenesis. Crystal structures of unphosphorylated and tyrosine64-phosphorylated Ras in complex with a BeF 3 - ground state analogue reveal "closed" Ras conformations very different from those of the "open" conformations previously observed for non-hydrolysable GTP analogue structures of Ras. They deliver new mechanistic and conformational insights into intrinsic GTP hydrolysis. Phosphorylation of tyrosine64 delivers conformational changes distant from the active site, showing why phosphorylated Ras has reduced affinity to its downstream effector Raf. 19 F NMR provides evidence for changes in the intrinsic GTPase and nucleotide exchange rate and identifies the concurrent presence of a major "closed" conformation alongside a minor yet functionally important "open" conformation at the ground state of Ras. This study expands the application of metal fluoride complexes in revealing major and minor conformational changes of dynamic and modified Ras proteins.


  • Organizational Affiliation

    School of Chemistry, Cardiff University, Park Place, Cardiff, CF10 3AT, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
GTPase HRasA [auth R]166Homo sapiensMutation(s): 0 
Gene Names: HRASHRAS1
EC: 3.6.5.2
UniProt & NIH Common Fund Data Resources
Find proteins for P01112 (Homo sapiens)
Explore P01112 
Go to UniProtKB:  P01112
PHAROS:  P01112
GTEx:  ENSG00000174775 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01112
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.32 Å
  • R-Value Free: 0.174 
  • R-Value Work: 0.135 
  • Space Group: H 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 92.662α = 90
b = 92.662β = 90
c = 119.323γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
Aimlessdata scaling
DIALSdata reduction
MOLREPphasing
Cootmodel building

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Wellcome TrustUnited Kingdom218568/Z/19/Z

Revision History  (Full details and data files)

  • Version 1.0: 2023-09-27
    Type: Initial release
  • Version 1.1: 2024-04-10
    Changes: Database references