1D4T

CRYSTAL STRUCTURE OF THE XLP PROTEIN SAP IN COMPLEX WITH A SLAM PEPTIDE

Summary for 1D4T

• Entry DOI: 10.2210/pdb1d4t/pdb
• Related: 1D1Z 1D4W
• Descriptor: T CELL SIGNAL TRANSDUCTION MOLECULE SAP, SIGNALING LYMPHOCYTIC ACTIVATION MOLECULE (3 entities in total)
• Functional Keywords: sh2 domain, tyrosine kinase, signal transduction, peptide recognition, signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm : O60880; Cell membrane ; Single-pass type I membrane protein. Isoform 3: Secreted . Isoform 4: Cell membrane : Q13291
• Total number of polymer chains: 2
• Total formula weight: 12982.91

Authors

Poy, F.,Yaffe, M.B.,Sayos, J.,Saxena, K.,Eck, M.J. (deposition date: 1999-10-06, release date: 1999-10-14, Last modification date: 2024-02-07)

Primary citation

Poy, F.,Yaffe, M.B.,Sayos, J.,Saxena, K.,Morra, M.,Sumegi, J.,Cantley, L.C.,Terhorst, C.,Eck, M.J.
Crystal structures of the XLP protein SAP reveal a class of SH2 domains with extended, phosphotyrosine-independent sequence recognition.
Mol.Cell, 4:555-561, 1999

PubMed 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).

PubMed: 10549287
DOI: 10.1016/S1097-2765(00)80206-3

Experimental method

X-RAY DIFFRACTION (1.1 Å)