1d4w
From Proteopedia
(New page: 200px<br /> <applet load="1d4w" size="450" color="white" frame="true" align="right" spinBox="true" caption="1d4w, resolution 1.8Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1d4w.gif|left|200px]]<br /> | + | [[Image:1d4w.gif|left|200px]]<br /><applet load="1d4w" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1d4w" size=" | + | |
caption="1d4w, resolution 1.8Å" /> | caption="1d4w, resolution 1.8Å" /> | ||
'''CRYSTAL STRUCTURE OF THE XLP PROTEIN SAP IN COMPLEX WITH SLAM PHOSPHOPEPTIDE'''<br /> | '''CRYSTAL STRUCTURE OF THE XLP PROTEIN SAP IN COMPLEX WITH SLAM PHOSPHOPEPTIDE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | SAP, the product of the gene mutated in X-linked lymphoproliferative | + | SAP, the product of the gene mutated in X-linked lymphoproliferative syndrome (XLP), consists of a single SH2 domain that has been shown to bind the cytoplasmic tail of the lymphocyte coreceptor SLAM. Here we describe structures that show that SAP binds phosphorylated and nonphosphorylated SLAM peptides in a similar mode, with the tyrosine or phosphotyrosine residue inserted into the phosphotyrosine-binding pocket. We find that specific interactions with residues N-terminal to the tyrosine, in addition to more characteristic C-terminal interactions, stabilize the complexes. A phosphopeptide library screen and analysis of mutations identified in XLP patients confirm that these extended interactions are required for SAP function. Further, we show that SAP and the similar protein EAT-2 recognize the sequence motif TIpYXX(V/I). |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1D4W is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1D4W is a [http://en.wikipedia.org/wiki/Protein_complex 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=1D4W OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Eck, M | + | [[Category: Eck, M J.]] |
[[Category: Poy, F.]] | [[Category: Poy, F.]] | ||
[[Category: Saxena, K.]] | [[Category: Saxena, K.]] | ||
[[Category: Sayos, J.]] | [[Category: Sayos, J.]] | ||
| - | [[Category: Yaffe, M | + | [[Category: Yaffe, M B.]] |
[[Category: lymphoproliferative disease]] | [[Category: lymphoproliferative disease]] | ||
[[Category: peptide recognition]] | [[Category: peptide recognition]] | ||
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[[Category: signal transduction]] | [[Category: signal transduction]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:12:59 2008'' |
Revision as of 10:13, 21 February 2008
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CRYSTAL STRUCTURE OF THE XLP PROTEIN SAP IN COMPLEX WITH SLAM PHOSPHOPEPTIDE
Contents |
Overview
SAP, the product of the gene mutated in X-linked lymphoproliferative syndrome (XLP), consists of a single SH2 domain that has been shown to bind the cytoplasmic tail of the lymphocyte coreceptor SLAM. Here we describe structures that show that SAP binds phosphorylated and nonphosphorylated SLAM peptides in a similar mode, with the tyrosine or phosphotyrosine residue inserted into the phosphotyrosine-binding pocket. We find that specific interactions with residues N-terminal to the tyrosine, in addition to more characteristic C-terminal interactions, stabilize the complexes. A phosphopeptide library screen and analysis of mutations identified in XLP patients confirm that these extended interactions are required for SAP function. Further, we show that SAP and the similar protein EAT-2 recognize the sequence motif TIpYXX(V/I).
Disease
Known diseases associated with this structure: Amyloidosis, secondary, susceptibility to OMIM:[104770], Lymphoproliferative syndrome, X-linked OMIM:[300490]
About this Structure
1D4W is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structures of the XLP protein SAP reveal a class of SH2 domains with extended, phosphotyrosine-independent sequence recognition., Poy F, Yaffe MB, Sayos J, Saxena K, Morra M, Sumegi J, Cantley LC, Terhorst C, Eck MJ, Mol Cell. 1999 Oct;4(4):555-61. PMID:10549287
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