Analysis of Interactions Stabilized by Fusicoccin A Reveals an Expanded Suite of Potential 14–3–3 Binding Partners
| Autor: | Ananya Sengupta, James H. Frederich, Brian G. Miller, Josue Liriano |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Phosphopeptides
0301 basic medicine Computational biology Plasma protein binding 01 natural sciences Biochemistry Article 03 medical and health sciences chemistry.chemical_compound Peptide Library Humans Glycosides Binding site Peptide library chemistry.chemical_classification Binding Sites 010405 organic chemistry Chemistry Computational Biology Signal transducing adaptor protein General Medicine 0104 chemical sciences Amino acid 030104 developmental biology 14-3-3 Proteins Fusicoccin Phosphoprotein Exoribonucleases Molecular Medicine Phosphorylation Protein Binding |
| Zdroj: | ACS Chemical Biology. 15:305-310 |
| ISSN: | 1554-8937 1554-8929 |
| Popis: | Fusicoccin A (FC) is a diterpene glycoside that stabilizes protein–protein interactions (PPIs) between 14–3–3 adapter proteins and their phosphoprotein interaction partners. Recently, FC has gained attention for its pro-apoptotic and neuroprotective properties in cell culture. Although the exact molecular mechanism(s) is (are) unresolved, 14–3–3 PPIs are central to this activity. With the goal of refining the pharmacology of this chemotype, we conducted a systematic analysis of the structural features that govern FC-induced stabilization of 14–3–3 PPIs utilizing a C-terminal phosphorylation recognition motif. This study confirmed that a C-terminal amino acid with a small alkyl group is required for the interaction of FC at canonical C-terminal 14–3–3 PPI interfaces. Using bioinformatics, this structural insight was leveraged to assemble a database of 119 candidate 14–3–3 PPIs that can serve as targets for FC. This group includes a subset of proteins with experimentally determined C-terminal phosphosites that have not been explored as potential targets of FC. |
| Databáze: | OpenAIRE |
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