2FCI

Structural basis for the requirement of two phosphotyrosines in signaling mediated by Syk tyrosine kinase


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 50 
  • Conformers Submitted: 16 
  • Selection Criteria: Lack of NOE violations & correct main chain geometry 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

Structural basis for the requirement of two phosphotyrosine residues in signaling mediated by syk tyrosine kinase

Groesch, T.D.Zhou, F.Mattila, S.Geahlen, R.L.Post, C.B.

(2006) J Mol Biol 356: 1222-1236

  • DOI: https://doi.org/10.1016/j.jmb.2005.11.095
  • Primary Citation of Related Structures:  
    2FCI

  • PubMed Abstract: 

    The protein-tyrosine kinase Syk couples immune recognition receptors to multiple signal transduction pathways, including the mobilization of calcium and the activation of NFAT. The ability of Syk to regulate signaling is influenced by its phosphorylation on tyrosine residues within the linker B region. The phosphorylation of both Y342 and Y346 is necessary for optimal signaling from the B cell receptor for antigen. The SH2 domains of multiple signaling proteins share the ability to bind this doubly phosphorylated site. The NMR structure of the C-terminal SH2 domain of PLCgamma (PLCC) bound to a doubly phosphorylated Syk peptide reveals a novel mode of phosphotyrosine recognition. PLCC undergoes extensive conformational changes upon binding to form a second phosphotyrosine-binding pocket in which pY346 is largely desolvated and stabilized through electrostatic interactions. The formation of the second binding pocket is distinct from other modes of phosphotyrosine recognition in SH2-protein association. The dependence of signaling on simultaneous phosphorylation of these two tyrosine residues offers a new mechanism to fine-tune the cellular response to external stimulation.


  • Organizational Affiliation

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


Macromolecules

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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Doubly phosphorylated peptide derived from Syk kinase comprising residues 338-350A [auth B]14N/AMutation(s): 0 
UniProt
Find proteins for Q32PK0 (Bos taurus)
Explore Q32PK0 
Go to UniProtKB:  Q32PK0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ32PK0
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
C-termainl SH2 domain from phospholipase C-gamma-1 comprising residues 663-759B [auth A]105Bos taurusMutation(s): 0 
Gene Names: PLCG1
EC: 3.1.4.11
UniProt
Find proteins for P08487 (Bos taurus)
Explore P08487 
Go to UniProtKB:  P08487
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP08487
Sequence Annotations
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  • Reference Sequence
Small Molecules
Modified Residues  2 Unique
IDChains TypeFormula2D DiagramParent
GMA
Query on GMA
A [auth B]L-PEPTIDE LINKINGC5 H10 N2 O3GLU
PTR
Query on PTR
A [auth B]L-PEPTIDE LINKINGC9 H12 N O6 PTYR
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 50 
  • Conformers Submitted: 16 
  • Selection Criteria: Lack of NOE violations & correct main chain geometry 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-01-31
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2012-05-02
    Changes: Structure summary
  • Version 2.0: 2023-11-15
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations