3o8i | pdb_00003o8i

Structure of 14-3-3 isoform sigma in complex with a C-Raf1 peptide and a stabilizing small molecule fragment

spinqualitylabelsall models 3o8i, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3o8i is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: M1T, SEP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 1433S_HUMAN Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The Ras-RAF-MAPK pathway is overactive in many cancers and in some developmental disorders. In one of the latter, Noonan syndrome, nine activating C-RAF mutations cluster around Ser(259), a regulatory site for inhibition by 14-3-3 proteins. We show that these mutations impair binding of 14-3-3 proteins to C-RAF and alter its subcellular localization by promoting Ras-mediated plasma membrane recruitment of C-RAF. By providing biophysical binding data, the 14-3-3/C-RAFpS(259) crystal structure, and cellular analyses we present a mechanistic link between a well-described human developmental disorder and the impairment of a 14-3-3/target protein interaction. As a broader implication of these findings, modulating the C-RAFSer(259)/14-3-3 protein-protein interaction with a stabilizing small molecule may yield a novel potential approach for diseases resulting from an overactive Ras-RAF-MAPK pathway. Impaired binding of 14-3-3 to C-RAF in Noonan Syndrome implies new approaches in diseases with increased Ras signaling.,Molzan M, Schumacher B, Ottmann C, Baljuls A, Polzien L, Weyand M, Thiel P, Rose R, Rose M, Kuhenne P, Kaiser M, Rapp UR, Kuhlmann J, Ottmann C Mol Cell Biol. 2010 Aug 2. PMID:20679480 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also 14-3-3 protein 3D structures

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