1KA6

SAP/SH2D1A bound to peptide n-pY

1KA6 の概要

• エントリーDOI: 10.2210/pdb1ka6/pdb
• 関連するPDBエントリー: 1KA7
• NMR情報: BMRB: 5212
• 分子名称: SH2 DOMAIN PROTEIN 1A, peptide n-pY (2 entities in total)
• 機能のキーワード: sh2 domain, protein-peptide complex, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm (Probable): O60880; Cell membrane; Single-pass type I membrane protein: Q13291
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 15237.31

構造登録者

Hwang, P.M.,Li, C.,Morra, M.,Lillywhite, J.,Gertler, F.,Terhorst, C.,Kay, L.E.,Pawson, T.,Forman-Kay, J.,Li, S.-C. (登録日: 2001-10-31, 公開日: 2001-11-07, 最終更新日: 2021-10-27)

主引用文献

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

実験手法

SOLUTION NMR