Crystal structures of the XLP protein SAP reveal a class of SH2 domains with extended, phosphotyrosine-independent sequence recognition

Florence Poy, Michael B. Yaffe, Joan Sayos, Kumkum Saxena, Massimo Morra, Janos Sumegi, Lewis C. Cantley, Cox Terhorst, Michael J. Eck

Research output: Contribution to journalArticle

200 Scopus citations

Abstract

SAP, the product of the gene mutated in X-linked lymphoproliferative syndrome (XLP), consists of a single SH2 domain that has been shown to bind the cytoplasmic tail of the lymphocyte coreceptor SLAM. Here we describe structures that show that SAP binds phosphorylated and nonphosphorylated SLAM peptides in a similar mode, with the tyrosine or phosphotyrosine residue inserted into the phosphotyrosine-binding pocket. We find that specific interactions with residues N-terminal to the tyrosine, in addition to more characteristic C-terminal interactions, stabilize the complexes. A phosphopeptide library screen and analysis of mutations identified in XLP patients confirm that these extended interactions are required for SAP function. Further, we show that SAP and the similar protein EAT-2 recognize the sequence motif TIpYXX(V/I).

Original languageEnglish (US)
Pages (from-to)555-561
Number of pages7
JournalMolecular Cell
Volume4
Issue number4
DOIs
StatePublished - Oct 1999

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Crystal structures of the XLP protein SAP reveal a class of SH2 domains with extended, phosphotyrosine-independent sequence recognition'. Together they form a unique fingerprint.

  • Cite this

    Poy, F., Yaffe, M. B., Sayos, J., Saxena, K., Morra, M., Sumegi, J., Cantley, L. C., Terhorst, C., & Eck, M. J. (1999). Crystal structures of the XLP protein SAP reveal a class of SH2 domains with extended, phosphotyrosine-independent sequence recognition. Molecular Cell, 4(4), 555-561. https://doi.org/10.1016/S1097-2765(00)80206-3