1ka7

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[[Image:1ka7.gif|left|200px]]
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[[Image:1ka7.png|left|200px]]
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{{STRUCTURE_1ka7| PDB=1ka7 | SCENE= }}
{{STRUCTURE_1ka7| PDB=1ka7 | SCENE= }}
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'''SAP/SH2D1A bound to peptide n-Y-c'''
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===SAP/SH2D1A bound to peptide n-Y-c===
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==Overview==
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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.
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The line below this paragraph, {{ABSTRACT_PUBMED_11823424}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 11823424 is the PubMed ID number.
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{{ABSTRACT_PUBMED_11823424}}
==About this Structure==
==About this Structure==
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1KA7 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KA7 OCA].
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1KA7 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KA7 OCA].
==Reference==
==Reference==
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[[Category: Protein-peptide complex]]
[[Category: Protein-peptide complex]]
[[Category: Sh2 domain]]
[[Category: Sh2 domain]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 22:29:39 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 10:01:21 2008''

Revision as of 07:01, 2 July 2008

Image:1ka7.png

Template:STRUCTURE 1ka7

SAP/SH2D1A bound to peptide n-Y-c

Template:ABSTRACT PUBMED 11823424

About this Structure

1KA7 is a Protein complex structure of sequences from Homo sapiens. Full experimental 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

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