1m27
From Proteopedia
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|PDB= 1m27 |SIZE=350|CAPTION= <scene name='initialview01'>1m27</scene>, resolution 2.5Å | |PDB= 1m27 |SIZE=350|CAPTION= <scene name='initialview01'>1m27</scene>, resolution 2.5Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=FLC:CITRATE ANION'>FLC</scene> | + | |LIGAND= <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1d4t|1D4T]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1m27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m27 OCA], [http://www.ebi.ac.uk/pdbsum/1m27 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1m27 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=104770 104770]], Lymphoproliferative syndrome, X-linked OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300490 300490]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Song, H K.]] | [[Category: Song, H K.]] | ||
[[Category: Terhorst, C.]] | [[Category: Terhorst, C.]] | ||
| - | [[Category: FLC]] | ||
[[Category: sh2-sh3 interaction]] | [[Category: sh2-sh3 interaction]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:10:20 2008'' |
Revision as of 19:10, 30 March 2008
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| , resolution 2.5Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 | ||||||
| Related: | 1D4T
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of SAP/FynSH3/SLAM ternary complex
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.
About this Structure
1M27 is a Protein complex structure of sequences from Homo sapiens. 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
Page seeded by OCA on Sun Mar 30 22:10:20 2008
