6vro
The structure of the PP2A B56 subunit AIM1 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 PubMedThe recruitment of substrates by the ser/thr protein phosphatase 2A (PP2A) is poorly understood, limiting our understanding of PP2A-regulated signaling. Recently, the first PP2A:B56 consensus binding motif, LxxIxE, was identified. However, most validated LxxIxE motifs bind PP2A:B56 with micromolar affinities, suggesting that additional motifs exist to enhance PP2A:B56 binding. Here, we report the requirement of a positively charged motif in a subset of PP2A:B56 interactors, including KIF4A, to facilitate B56 binding via dynamic, electrostatic interactions. Using molecular and cellular experiments, we show that a conserved, negatively charged groove on B56 mediates dynamic binding. We also discovered that this positively charged motif, in addition to facilitating KIF4A dephosphorylation, is essential for condensin I binding, a function distinct and exclusive from PP2A-B56 binding. Together, these results reveal how dynamic, charge-charge interactions fine-tune the interactions mediated by specific motifs, providing a new framework for understanding how PP2A regulation drives cellular signaling. A dynamic charge-charge interaction modulates PP2A:B56 substrate recruitment.,Wang X, Garvanska DH, Nasa I, Ueki Y, Zhang G, Kettenbach AN, Peti W, Nilsson J, Page R Elife. 2020 Mar 20;9. pii: 55966. doi: 10.7554/eLife.55966. PMID:32195664[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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