1M27

Crystal structure of SAP/FynSH3/SLAM ternary complex

Summary for 1M27

• Entry DOI: 10.2210/pdb1m27/pdb
• Related: 1D4T
• Descriptor: SH2 domain protein 1A, Signaling lymphocytic activation molecule, Proto-oncogene tyrosine-protein kinase FYN, ... (5 entities in total)
• Functional Keywords: sh2-sh3 interaction, signaling protein, transferase
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm (Probable): O60880; Cell membrane: P06241; Cell membrane; Single-pass type I membrane protein: Q13291
• Total number of polymer chains: 3
• Total formula weight: 20110.52

Authors

Chan, B.,Griesbach, J.,Song, H.K.,Poy, F.,Terhorst, C.,Eck, M.J. (deposition date: 2002-06-21, release date: 2003-05-06, Last modification date: 2024-02-14)

Primary citation

Chan, B.,Lanyi, A.,Song, H.K.,Griesbach, J.,Simarro-Grande, M.,Poy, F.,Howie, D.,Sumegi, J.,Terhorst, C.,Eck, M.J.
SAP couples Fyn to SLAM immune receptors.
NAT.CELL BIOL., 5:155-160, 2003

PubMed Abstract: 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.

PubMed: 12545174
DOI: 10.1038/ncb920

Experimental method

X-RAY DIFFRACTION (2.5 Å)