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From Proteopedia
14-3-3sigma in complex with SLP76pS376 phosphopeptide crystal structure
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 SH2 domain-containing protein of 76 kDa, SLP76, is an important adaptor protein that coordinates a complex protein network downstream of T-cell receptors (TCR), ultimately regulating the immune response. Upon phosphorylation on Ser376, SLP76 interacts with 14-3-3 adaptor proteins, which leads to its proteolytic degradation. This provides a negative feedback mechanism by which TCR signalling can be controlled. To gain insight into the 14-3-3/SLP76 protein-protein interaction (PPI), we have determined a high-resolution crystal structure of a SLP76 synthetic peptide containing Ser376 with 14-3-3sigma. We then characterized its binding to 14-3-3 proteins biophysically by means of fluorescence polarization and isothermal titration calorimetry. Furthermore, we generated two recombinant SLP76 protein constructs and characterized their binding to 14-3-3. Our work lays the foundation for drug design efforts aimed at targeting the 14-3-3/SLP76 interaction and, thereby, TCR signalling. The 14-3-3/SLP76 protein-protein interaction in T-cell receptor signalling: a structural and biophysical characterization.,Soini L, Leysen S, Davis J, Westwood M, Ottmann C FEBS Lett. 2021 Feb;595(3):404-414. doi: 10.1002/1873-3468.13993. Epub 2020 Nov , 22. PMID:33159816[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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