1r1s

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spinqualitylabelsall models PDB ID 1r1s Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 1.90Å
Ligands:	, ,
Gene:	GADS (Mus musculus)
Related:	1R1P, 1R1Q
Resources:	FirstGlance, OCA, PDBsum, RCSB
Coordinates:	save as pdb, mmCIF, xml

Structural Basis for Differential Recognition of Tyrosine Phosphorylated Sites in the Linker for Activation of T cells (LAT) by the Adaptor Protein Gads

Overview

The transmembrane protein, linker for activation of T cells (LAT), is essential for T-cell activation and development. Phosphorylation of LAT at multiple tyrosines creates binding sites for the adaptors Gads and Grb2, leading to nucleation of multiprotein signaling complexes. Human LAT contains five potential binding sites for Gads, of which only those at Tyr171 and Tyr191 appear necessary for T-cell function. We asked whether Gads binds preferentially to these sites, as differential recognition could assist in assembling defined LAT-based complexes. Measured calorimetrically, Gads-SH2 binds LAT tyrosine phosphorylation sites 171 and 191 with higher affinities than the other sites, with the differences ranging from only several fold weaker binding to no detectable interaction. Crystal structures of Gads-SH2 complexed with phosphopeptides representing sites 171, 191 and 226 were determined to 1.8-1.9 A resolutions. The structures reveal the basis for preferential recognition of specific LAT sites by Gads, as well as for the relatively greater promiscuity of the related adaptor Grb2, whose binding also requires asparagine at position +2 C-terminal to the phosphorylated tyrosine.

About this Structure

1R1S is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

Reference

Structural basis for differential recognition of tyrosine-phosphorylated sites in the linker for activation of T cells (LAT) by the adaptor Gads., Cho S, Velikovsky CA, Swaminathan CP, Houtman JC, Samelson LE, Mariuzza RA, EMBO J. 2004 Apr 7;23(7):1441-51. Epub 2004 Mar 18. PMID:15029250

Page seeded by OCA on Sun Mar 30 23:22:01 2008