1KA6

SAP/SH2D1A bound to peptide n-pY

Summary for 1KA6

• Entry DOI: 10.2210/pdb1ka6/pdb
• Related: 1KA7
• NMR Information: BMRB: 5212
• Descriptor: SH2 DOMAIN PROTEIN 1A, peptide n-pY (2 entities in total)
• Functional Keywords: sh2 domain, protein-peptide complex, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm (Probable): O60880; Cell membrane; Single-pass type I membrane protein: Q13291
• Total number of polymer chains: 2
• Total formula weight: 15237.31

Authors

Hwang, P.M.,Li, C.,Morra, M.,Lillywhite, J.,Gertler, F.,Terhorst, C.,Kay, L.E.,Pawson, T.,Forman-Kay, J.,Li, S.-C. (deposition date: 2001-10-31, release date: 2001-11-07, Last modification date: 2021-10-27)

Primary citation

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.
A "three-pronged" binding mechanism for the SAP/SH2D1A SH2 domain: structural basis and relevance to the XLP syndrome.
EMBO J., 21:314-323, 2002

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.

PubMed: 11823424
DOI: 10.1093/emboj/21.3.314

Experimental method

SOLUTION NMR