8dgp
14-3-3 epsilon bound to phosphorylated PEAK3 (pS69) peptide
Structural highlights
Disease1433E_HUMAN Distal 17p13.3 microdeletion syndrome;17p13.3 microduplication syndrome;Miller-Dieker syndrome. Function1433E_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. Publication Abstract from PubMedPEAK pseudokinases regulate cell migration, invasion and proliferation by recruiting key signaling proteins to the cytoskeleton. Despite lacking catalytic activity, alteration in their expression level is associated with several aggressive cancers. Here, we elucidate the molecular details of key PEAK signaling interactions with the adapter proteins CrkII and Grb2 and the scaffold protein 14-3-3. Our findings rationalize why the dimerization of PEAK proteins has a crucial function in signal transduction and provide biophysical and structural data to unravel binding specificity within the PEAK interactome. We identify a conserved high affinity 14-3-3 motif on PEAK3 and demonstrate its role as a molecular switch to regulate CrkII binding and signaling via Grb2. Together, our studies provide a detailed structural snapshot of PEAK interaction networks and further elucidate how PEAK proteins, especially PEAK3, act as dynamic scaffolds that exploit adapter proteins to control signal transduction in cell growth/motility and cancer. Structural mapping of PEAK pseudokinase interactions identifies 14-3-3 as a molecular switch for PEAK3 signaling.,Roy MJ, Surudoi MG, Kropp A, Hou J, Dai W, Hardy JM, Liang LY, Cotton TR, Lechtenberg BC, Dite TA, Ma X, Daly RJ, Patel O, Lucet IS Nat Commun. 2023 Jun 19;14(1):3542. doi: 10.1038/s41467-023-38869-9. PMID:37336884[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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