8r0z
From Proteopedia
14-3-3 sigma in complex with TAZ peptide and stabilizing fragment TCF199
Structural highlights
Function1433S_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. Publication Abstract from PubMedThe identification of chemical starting points for the development of molecular glues is challenging. Here, we employed fragment screening and identified an allosteric stabilizer of the complex between 14-3-3 and a TAZ-derived peptide. The fragment binds preferentially to the 14-3-3/TAZ peptide complex and shows moderate stabilization in differential scanning fluorimetry and microscale thermophoresis. The binding site of the fragment was predicted by molecular dynamics calculations to be distant from the 14-3-3/TAZ peptide interface, located between helices 8 and 9 of the 14-3-3 protein. This site was confirmed by nuclear magnetic resonance and X-ray protein crystallography, revealing the first example of an allosteric stabilizer for 14-3-3 protein-protein interactions. Fragment-Based Interrogation of the 14-3-3/TAZ Protein-Protein Interaction.,Andlovic B, Valenti D, Centorrino F, Picarazzi F, Hristeva S, Hiltmann M, Wolf A, Cantrelle FX, Mori M, Landrieu I, Levy LM, Klebl B, Tzalis D, Genski T, Eickhoff J, Ottmann C Biochemistry. 2024 Sep 3;63(17):2196-2206. doi: 10.1021/acs.biochem.4c00248. Epub , 2024 Aug 22. PMID:39172504[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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