5swf | pdb_00005swf
The structure of the PP2A B56 subunit double phosphorylated BubR1 complex
Structural highlights
Function2A5G_HUMAN The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment. The PP2A-PPP2R5C holoenzyme may specifically dephosphorylate and activate TP53 and play a role in DNA damage-induced inhibition of cell proliferation. PP2A-PPP2R5C may also regulate the ERK signaling pathway through ERK dephosphorylation.[1] [2] Publication Abstract from PubMedSpecific interactions between proteins govern essential physiological processes including signaling. Many enzymes, especially the family of serine/threonine phosphatases (PSPs: PP1, PP2A, and PP2B/calcineurin/CN), recruit substrates and regulatory proteins by binding short linear motifs (SLiMs), short sequences found within intrinsically disordered regions that mediate specific protein-protein interactions. While tremendous progress had been made in identifying where and how SLiMs bind PSPs, especially PP1 and CN, essentially nothing is known about how SLiMs bind PP2A, a validated cancer drug target. Here we describe three structures of a PP2A-SLiM interaction (B56:pS-RepoMan, B56:pS-BubR1, and B56:pSpS-BubR1), show that this PP2A-specific SLiM is defined as LSPIxE, and then use these data to discover scores of likely PP2A regulators and substrates. Together, these data provide a powerful approach not only for dissecting PP2A interaction networks in cells but also for targeting PP2A diseases, such as cancer. Expanding the PP2A Interactome by Defining a B56-Specific SLiM.,Wang X, Bajaj R, Bollen M, Peti W, Page R Structure. 2016 Dec 6;24(12):2174-2181. doi: 10.1016/j.str.2016.09.010. Epub 2016, Oct 27. PMID:27998540[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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