{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":48,"searchCount":0},"additional":{"submitter":["Wang X"],"funding":["National Institute of Neurological Disorders and Stroke","Independent Research Fund Denmark","Novo Nordisk","Novo Nordisk Foundation Center for Protein Research","Novo Nordisk Fonden","National Institute of General Medical Sciences"],"pagination":["e55966"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7108865"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9"],"pubmed_abstract":["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."],"journal":["eLife"],"pubmed_title":["A dynamic charge-charge interaction modulates PP2A:B56 substrate recruitment."],"pmcid":["PMC7108865"],"funding_grant_id":["PI Jakob Nilsson","R01GM098482","NNF14CC0001","R01NS091336","DFF-7016-00086","P20GM113132","R35GM119455","R01GM134683"],"pubmed_authors":["Zhang G","Nilsson J","Kettenbach AN","Peti W","Ueki Y","Wang X","Page R","Nasa I","Garvanska DH"],"view_count":["48"],"additional_accession":[]},"is_claimable":false,"name":"A dynamic charge-charge interaction modulates PP2A:B56 substrate recruitment.","description":"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.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Mar","modification":"2024-10-19T11:36:04.992Z","creation":"2020-05-22T15:30:27Z"},"accession":"S-EPMC7108865","cross_references":{"pubmed":["32195664"],"doi":["10.7554/eLife.55966"]}}