2LCT

Solution structure of the Vav1 SH2 domain complexed with a Syk-derived doubly phosphorylated peptide


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the least restraint violations 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Two closely spaced tyrosines regulate NFAT signaling in B cells via Syk association with Vav.

Chen, C.H.Martin, V.A.Gorenstein, N.M.Geahlen, R.L.Post, C.B.

(2011) Mol Cell Biol 31: 2984-2996

  • DOI: https://doi.org/10.1128/MCB.05043-11
  • Primary Citation of Related Structures:  
    2LCT

  • PubMed Abstract: 

    Activated Syk, an essential tyrosine kinase in B cell signaling, interacts with Vav guanine nucleotide exchange factors and regulates Vav activity through tyrosine phosphorylation. The Vav SH2 domain binds Syk linker B by an unusual recognition of two closely spaced Syk tyrosines: Y342 and Y346. The binding affinity is highest when both Y342 and Y346 are phosphorylated. An investigation in B cells of the dependence of Vav phosphorylation and NFAT activation on phosphorylation of Y342 and Y346 finds that cellular response levels match the relative binding affinities of the Vav1 SH2 domain for singly and doubly phosphorylated linker B peptides. This key result suggests that the uncommon recognition determinant of these two closely spaced tyrosines is a limiting factor in signaling. Interestingly, differences in affinities for binding singly and doubly phosphorylated peptides are reflected in the on rate, not the off rate. Such a control mechanism would be highly effective for regulating binding among competing Syk binding partners. The nuclear magnetic resonance (NMR) structure of Vav1 SH2 in complex with a doubly phosphorylated linker B peptide reveals diverse conformations associated with the unusual SH2 recognition of two phosphotyrosines. NMR relaxation indicates compensatory changes in loop fluctuations upon binding, with implications for nonphosphotyrosine interactions of Vav1 SH2.


  • Organizational Affiliation

    Department of Medicinal Chemistry and Molecular Pharmacology, Markey Center for Structural Biology and Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Proto-oncogene vav107Homo sapiensMutation(s): 0 
Gene Names: VAVVAV1
UniProt & NIH Common Fund Data Resources
Find proteins for P15498 (Homo sapiens)
Explore P15498 
Go to UniProtKB:  P15498
PHAROS:  P15498
GTEx:  ENSG00000141968 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP15498
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Tyrosine-protein kinase SYK13Mus musculusMutation(s): 0 
EC: 2.7.10.2
UniProt & NIH Common Fund Data Resources
Find proteins for P48025 (Mus musculus)
Explore P48025 
Go to UniProtKB:  P48025
IMPC:  MGI:99515
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP48025
Sequence Annotations
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  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PTR
Query on PTR
B
L-PEPTIDE LINKINGC9 H12 N O6 PTYR
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the least restraint violations 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-06-01
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2012-05-23
    Changes: Database references
  • Version 1.3: 2023-06-14
    Changes: Data collection, Database references, Derived calculations, Other