MassIVE MSV000083785

Complete Public PXD013886

A dynamic charge:charge interaction modulates PP2A:B56 interactions

Description

The recruitment of specific substrates by ser/thr protein phosphatase 2A (PP2A) regulatory B-subunits is poorly understood, limiting our understanding of PP2A-regulated signaling. Recently, the first PP2A:B56 consensus binding motif, LxxIxE, which confers substrate specificity to PP2A:B56 holoenzymes, was identified. However, most validated LxxIxE motifs interact with PP2A:B56 with low micromolar affinities, suggesting that additional recognition motifs exist that function cooperatively to enhance PP2A:B56 binding. Here, we report the requirement of a positively charged motif in a subset of PP2A:B56 interactors that facilitates B56 binding via dynamic charge:charge interactions. Using molecular and cellular approaches, we show that a highly conserved, negatively charged groove on B56 mediates this dynamic interaction. We also show that this motif is required for efficient binding and dephosphorylation of KIF4A in cells, confirming the functional relevance of this motif for PP2A:B56 dephosphorylation. Collectively our results provide an important framework for understanding PP2A regulation of cellular signaling. [doi:10.25345/C5HK9F] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: PP2A ; B56 ; phosphatase ; LxxIxE ; motif ; charge ; interaction ; KIF4A ; cellular signaling ; holoenzyme

Contact

Principal Investigators: Arminja Kettenbach, The Geisel School of Medicine at Dartmouth, United States
Submitting User: madamo
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