1m27

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Revision as of 16:00, 12 November 2007

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spinqualitylabelsall models 1m27, resolution 2.5Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of SAP/FynSH3/SLAM ternary complex

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

SAP (SLAM-associated protein) is a small lymphocyte-specific signalling, molecule that is defective or absent in patients with X-linked, lymphoproliferative syndrome (XLP). Consistent with its single src, homology 2 (SH2) domain architecture and unusually high affinity for SLAM, (also called CD150), SAP has been suggested to function by blocking, binding of SHP-2 or other SH2-containing signalling proteins to SLAM, receptors. Additionally, SAP has recently been shown to be required for, recruitment and activation of the Src-family kinase FynT after SLAM, ligation. This signalling 'adaptor' function has been difficult to, conceptualize, because unlike typical SH2-adaptor proteins, SAP contains, only a single SH2 domain and lacks other recognized protein interaction, domains or motifs. Here, we show that the SAP SH2 domain binds to the SH3, domain of FynT and directly couples FynT to SLAM. The crystal structure of, a ternary SLAM-SAP-Fyn-SH3 complex reveals that SAP binds the FynT SH3, domain through a surface-surface interaction that does not involve, canonical SH3 or SH2 binding interactions. The observed mode of binding to, the Fyn-SH3 domain is expected to preclude the auto-inhibited conformation, of Fyn, thereby promoting activation of the kinase after recruitment., These findings broaden our understanding of the functional repertoire of, SH3 and SH2 domains.

Disease

Known diseases associated with this structure: Amyloidosis, secondary, susceptibility to OMIM:[104770], Lymphoproliferative syndrome, X-linked OMIM:[300490]

About this Structure

1M27 is a Protein complex structure of sequences from Homo sapiens with FLC as ligand. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 Full crystallographic information is available from OCA.

Reference

SAP couples Fyn to SLAM immune receptors., Chan B, Lanyi A, Song HK, Griesbach J, Simarro-Grande M, Poy F, Howie D, Sumegi J, Terhorst C, Eck MJ, Nat Cell Biol. 2003 Feb;5(2):155-60. PMID:12545174

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