1KA7

SAP/SH2D1A bound to peptide n-Y-c


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Submitted: 

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This is version 1.3 of the entry. See complete history


Literature

A "three-pronged" binding mechanism for the SAP/SH2D1A SH2 domain: structural basis and relevance to the XLP syndrome.

Hwang, P.M.Li, C.Morra, M.Lillywhite, J.Muhandiram, D.R.Gertler, F.Terhorst, C.Kay, L.E.Pawson, T.Forman-Kay, J.D.Li, S.C.

(2002) EMBO J 21: 314-323

  • DOI: https://doi.org/10.1093/emboj/21.3.314
  • Primary Citation of Related Structures:  
    1KA6, 1KA7

  • PubMed Abstract: 

    The SH2 domain protein SAP/SH2D1A, encoded by the X-linked lymphoproliferative (XLP) syndrome gene, associates with the hematopoietic cell surface receptor SLAM in a phosphorylation-independent manner. By screening a repertoire of synthetic peptides, the specificity of SAP/SH2D1A has been mapped and a consensus sequence motif for binding identified, T/S-x-x-x-x-V/I, where x represents any amino acid. Remarkably, this motif contains neither a Tyr nor a pTyr residue, a hallmark of conventional SH2 domain-ligand interactions. The structures of the protein, determined by NMR, in complex with two distinct peptides provide direct evidence in support of a "three-pronged" binding mechanism for the SAP/SH2D1A SH2 domain in contrast to the "two-pronged" binding for conventional SH2 domains. Differences in the structures of the two complexes suggest considerable flexibility in the SH2 domain, as further confirmed and characterized by hydrogen exchange studies. The structures also explain binding defects observed in disease-causing SAP/SH2D1A mutants and suggest that phosphorylation-independent interactions mediated by SAP/SH2D1A likely play an important role in the pathogenesis of XLP.


  • Organizational Affiliation

    Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
SH2 DOMAIN PROTEIN 1A128Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for O60880 (Homo sapiens)
Explore O60880 
Go to UniProtKB:  O60880
PHAROS:  O60880
GTEx:  ENSG00000183918 
Entity Groups  
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UniProt GroupO60880
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
peptide n-Y-c12N/AMutation(s): 1 
UniProt & NIH Common Fund Data Resources
Find proteins for Q13291 (Homo sapiens)
Explore Q13291 
Go to UniProtKB:  Q13291
PHAROS:  Q13291
GTEx:  ENSG00000117090 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13291
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Submitted: 

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2001-11-07
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2021-10-27
    Changes: Database references, Derived calculations