1ka6
From Proteopedia
(New page: 200px<br /> <applet load="1ka6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ka6" /> '''SAP/SH2D1A bound to peptide n-pY'''<br /> ...) |
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| - | [[Image:1ka6.gif|left|200px]]<br /> | + | [[Image:1ka6.gif|left|200px]]<br /><applet load="1ka6" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1ka6" size=" | + | |
caption="1ka6" /> | caption="1ka6" /> | ||
'''SAP/SH2D1A bound to peptide n-pY'''<br /> | '''SAP/SH2D1A bound to peptide n-pY'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The SH2 domain protein SAP/SH2D1A, encoded by the X-linked | + | The SH2 domain protein SAP/SH2D1A, encoded by the X-linked lymphoproliferative (XLP) syndrome gene, associates with the hematopoietic cell surface receptor SLAM in a phosphorylation-independent manner. By screening a repertoire of synthetic peptides, the specificity of SAP/SH2D1A has been mapped and a consensus sequence motif for binding identified, T/S-x-x-x-x-V/I, where x represents any amino acid. Remarkably, this motif contains neither a Tyr nor a pTyr residue, a hallmark of conventional SH2 domain-ligand interactions. The structures of the protein, determined by NMR, in complex with two distinct peptides provide direct evidence in support of a "three-pronged" binding mechanism for the SAP/SH2D1A SH2 domain in contrast to the "two-pronged" binding for conventional SH2 domains. Differences in the structures of the two complexes suggest considerable flexibility in the SH2 domain, as further confirmed and characterized by hydrogen exchange studies. The structures also explain binding defects observed in disease-causing SAP/SH2D1A mutants and suggest that phosphorylation-independent interactions mediated by SAP/SH2D1A likely play an important role in the pathogenesis of XLP. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1KA6 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1KA6 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KA6 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Forman-Kay, J.]] | [[Category: Forman-Kay, J.]] | ||
[[Category: Gertler, F.]] | [[Category: Gertler, F.]] | ||
| - | [[Category: Hwang, P | + | [[Category: Hwang, P M.]] |
| - | [[Category: Kay, L | + | [[Category: Kay, L E.]] |
[[Category: Li, C.]] | [[Category: Li, C.]] | ||
| - | [[Category: Li, S | + | [[Category: Li, S C.]] |
[[Category: Lillywhite, J.]] | [[Category: Lillywhite, J.]] | ||
[[Category: Morra, M.]] | [[Category: Morra, M.]] | ||
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[[Category: sh2 domain]] | [[Category: sh2 domain]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:31:49 2008'' |
Revision as of 11:31, 21 February 2008
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SAP/SH2D1A bound to peptide n-pY
Contents |
Overview
The SH2 domain protein SAP/SH2D1A, encoded by the X-linked lymphoproliferative (XLP) syndrome gene, associates with the hematopoietic cell surface receptor SLAM in a phosphorylation-independent manner. By screening a repertoire of synthetic peptides, the specificity of SAP/SH2D1A has been mapped and a consensus sequence motif for binding identified, T/S-x-x-x-x-V/I, where x represents any amino acid. Remarkably, this motif contains neither a Tyr nor a pTyr residue, a hallmark of conventional SH2 domain-ligand interactions. The structures of the protein, determined by NMR, in complex with two distinct peptides provide direct evidence in support of a "three-pronged" binding mechanism for the SAP/SH2D1A SH2 domain in contrast to the "two-pronged" binding for conventional SH2 domains. Differences in the structures of the two complexes suggest considerable flexibility in the SH2 domain, as further confirmed and characterized by hydrogen exchange studies. The structures also explain binding defects observed in disease-causing SAP/SH2D1A mutants and suggest that phosphorylation-independent interactions mediated by SAP/SH2D1A likely play an important role in the pathogenesis of XLP.
Disease
Known diseases associated with this structure: Amyloidosis, secondary, susceptibility to OMIM:[104770], Lymphoproliferative syndrome, X-linked OMIM:[300490]
About this Structure
1KA6 is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
A "three-pronged" binding mechanism for the SAP/SH2D1A SH2 domain: structural basis and relevance to the XLP syndrome., Hwang PM, Li C, Morra M, Lillywhite J, Muhandiram DR, Gertler F, Terhorst C, Kay LE, Pawson T, Forman-Kay JD, Li SC, EMBO J. 2002 Feb 1;21(3):314-23. PMID:11823424
Page seeded by OCA on Thu Feb 21 13:31:49 2008
