3CLY

Crystal Structure of FGF Receptor 2 (FGFR2) Kinase Domains Trapped in Trans-Phosphorylation Reaction


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.216 

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This is version 1.5 of the entry. See complete history


Literature

A crystallographic snapshot of tyrosine trans-phosphorylation in action

Chen, H.Xu, C.F.Ma, J.Eliseenkova, A.V.Li, W.Pollock, P.M.Pitteloud, N.Miller, W.T.Neubert, T.A.Mohammadi, M.

(2008) Proc Natl Acad Sci U S A 105: 19660-19665

  • DOI: https://doi.org/10.1073/pnas.0807752105
  • Primary Citation of Related Structures:  
    3CLY

  • PubMed Abstract: 

    Tyrosine trans-phosphorylation is a key event in receptor tyrosine kinase signaling, yet, the structural basis for this process has eluded definition. Here, we present the crystal structure of the FGF receptor 2 kinases caught in the act of trans-phosphorylation of Y769, the major C-terminal phosphorylation site. The structure reveals that enzyme- and substrate-acting kinases engage each other through elaborate and specific interactions not only in the immediate vicinity of Y769 and the enzyme active site, but also in regions that are as much of 18 A away from D626, the catalytic base in the enzyme active site. These interactions lead to an unprecedented level of specificity and precision during the trans-phosphorylation on Y769. Time-resolved mass spectrometry analysis supports the observed mechanism of trans-phosphorylation. Our data provide a molecular framework for understanding the mechanism of action of Kallmann syndrome mutations and the order of trans-phosphorylation reactions in FGFRs. We propose that the salient mechanistic features of Y769 trans-phosphorylation are applicable to trans-phosphorylation of the equivalent major phosphorylation sites in many other RTKs.


  • Organizational Affiliation

    Department of Pharmacology and Kimmel Center for Biology and Medicine at Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Fibroblast growth factor receptor 2334Homo sapiensMutation(s): 1 
Gene Names: FGFR2BEKKGFRKSAM
EC: 2.7.10.1
UniProt & NIH Common Fund Data Resources
Find proteins for P21802 (Homo sapiens)
Explore P21802 
Go to UniProtKB:  P21802
PHAROS:  P21802
GTEx:  ENSG00000066468 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP21802
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PTR
Query on PTR
A
L-PEPTIDE LINKINGC9 H12 N O6 PTYR
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.216 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.437α = 90
b = 68.462β = 90
c = 85.711γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
AMoREphasing
CNSrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-02-03
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2012-03-07
    Changes: Non-polymer description
  • Version 1.3: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.4: 2023-08-30
    Changes: Data collection, Refinement description
  • Version 1.5: 2023-11-15
    Changes: Data collection