TY - JOUR TI - A dynamic charge-charge interaction modulates PP2A:B56 substrate recruitment AU - Wang, Xinru AU - Garvanska, Dimitriya H AU - Nasa, Isha AU - Ueki, Yumi AU - Zhang, Gang AU - Kettenbach, Arminja N AU - Peti, Wolfgang AU - Nilsson, Jakob AU - Page, Rebecca A2 - Hunter, Tony A2 - Ron, David VL - 9 PY - 2020 DA - 2020/03/20 SP - e55966 C1 - eLife 2020;9:e55966 DO - 10.7554/eLife.55966 UR - https://doi.org/10.7554/eLife.55966 AB - The 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. KW - protein phosphatase KW - PP2A-B56 KW - intrinsically disordered protein KW - dynamic, charge-charge interactions KW - KIF4A KW - structural and cell biology JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -