1D4W: CRYSTAL STRUCTURE OF THE XLP PROTEIN SAP IN COMPLEX WITH SLAM PHOSPHOPEPTIDE

Citation:
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).
PDB ID: 1D4WDownload
MMDB ID: 11375
PDB Deposition Date: 1999/10/6
Updated in MMDB: 1999/11
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 1D4W: dimeric; determined by software (PISA)
Molecular Components in 1D4W
Label Count Molecule
Proteins (2 molecules)
1
T Cell Signal Transduction Molecule SAP(Gene symbol: SH2D1A)
Molecule annotation
1
Signaling Lymphocytic Activation Molecule(Gene symbol: SLAMF1)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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