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| - | [[Image:1ywt.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1ywt.png|left|200px]] |
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| | {{STRUCTURE_1ywt| PDB=1ywt | SCENE= }} | | {{STRUCTURE_1ywt| PDB=1ywt | SCENE= }} |
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| - | '''Crystal structure of the human sigma isoform of 14-3-3 in complex with a mode-1 phosphopeptide'''
| + | ===Crystal structure of the human sigma isoform of 14-3-3 in complex with a mode-1 phosphopeptide=== |
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| - | ==Overview==
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| - | The 14-3-3 family of proteins includes seven isotypes in mammalian cells that play numerous diverse roles in intracellular signaling. Most 14-3-3 proteins form homodimers and mixed heterodimers between different isotypes, with overlapping roles in ligand binding. In contrast, one mammalian isoform, 14-3-3sigma, expressed primarily in epithelial cells, appears to play a unique role in the cellular response to DNA damage and in human oncogenesis. The biological and structural basis for these 14-3-3sigma-specific functions is unknown. We demonstrate that endogenous 14-3-3sigma preferentially forms homodimers in cells. We have solved the x-ray crystal structure of 14-3-3sigma bound to an optimal phosphopeptide ligand at 2.4 angstroms resolution. The structure reveals the presence of stabilizing ring-ring and salt bridge interactions unique to the 14-3-3sigma homodimer structure and potentially destabilizing electrostatic interactions between subunits in 14-3-3sigma-containing heterodimers, rationalizing preferential homodimerization of 14-3-3sigma in vivo. The interaction of the phosphopeptide with 14-3-3 reveals a conserved mechanism for phospho-dependent ligand binding, implying that the phosphopeptide binding cleft is not the critical determinant of the unique biological properties of 14-3-3sigma. Instead, the structure suggests a second ligand binding site involved in 14-3-3sigma-specific ligand discrimination. We have confirmed this by site-directed mutagenesis of three sigma-specific residues that uniquely define this site. Mutation of these residues to the alternative sequence that is absolutely conserved in all other 14-3-3 isotypes confers upon 14-3-3sigma the ability to bind to Cdc25C, a ligand that is known to bind to other 14-3-3 proteins but not to sigma. | + | The line below this paragraph, {{ABSTRACT_PUBMED_15731107}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 15731107 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_15731107}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: 14-3-3]] | | [[Category: 14-3-3]] |
| | [[Category: Protein-phosphopeptide complex]] | | [[Category: Protein-phosphopeptide complex]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:53:44 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 08:30:04 2008'' |
Revision as of 05:30, 29 July 2008
Template:STRUCTURE 1ywt
Crystal structure of the human sigma isoform of 14-3-3 in complex with a mode-1 phosphopeptide
Template:ABSTRACT PUBMED 15731107
About this Structure
1YWT is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
A structural basis for 14-3-3sigma functional specificity., Wilker EW, Grant RA, Artim SC, Yaffe MB, J Biol Chem. 2005 May 13;280(19):18891-8. Epub 2005 Feb 24. PMID:15731107
Page seeded by OCA on Tue Jul 29 08:30:04 2008
