The Structural Basis for 14-3-3:Phosphopeptide Binding Specificity
| Autor: | Alastair Aitken, Stefano Volinia, Stephen J. Smerdon, Henrik Leffers, Michael B. Yaffe, Lewis C. Cantley, Paul R. Caron, Steven J. Gamblin, Katrin Rittinger |
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| Rok vydání: | 1997 |
| Předmět: |
Models
Molecular Phosphopeptides Tyrosine 3-Monooxygenase Protein Conformation Stereochemistry Molecular Sequence Data Plasma protein binding Biology Crystallography X-Ray General Biochemistry Genetics and Molecular Biology Substrate Specificity Turn (biochemistry) Phosphoserine chemistry.chemical_compound Protein structure Peptide Library Humans Enzyme Inhibitors Phosphorylation Peptide library 14-3-3 protein Binding selectivity Biochemistry Genetics and Molecular Biology(all) Proteins Phosphoserine Motif 14-3-3 Proteins chemistry Biochemistry Protein Binding |
| Zdroj: | Cell. 91:961-971 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/s0092-8674(00)80487-0 |
| Popis: | The 14-3-3 family of proteins mediates signal transduction by binding to phosphoserine-containing proteins. Using phosphoserine-oriented peptide libraries to probe all mammalian and yeast 14-3-3s, we identified two different binding motifs, RSXpSXP and RXY/FXpSXP, present in nearly all known 14-3-3 binding proteins. The crystal structure of 14-3-3ζ complexed with the phosphoserine motif in polyoma middle-T was determined to 2.6 Å resolution. The bound peptide is in an extended conformation, with a tight turn created by the pS +2 Pro in a cis conformation. Sites of peptide–protein interaction in the complex rationalize the peptide library results. Finally, we show that the 14-3-3 dimer binds tightly to single molecules containing tandem repeats of phosphoserine motifs, implicating bidentate association as a signaling mechanism with molecules such as Raf, BAD, and Cbl. |
| Databáze: | OpenAIRE |
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