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dc.contributor.authorWang, Xinru
dc.contributor.authorGarvanska, Dimitriya H
dc.contributor.authorNasa, Isha
dc.contributor.authorUeki, Yumi
dc.contributor.authorZhang, Gang
dc.contributor.authorKettenbach, Arminja N
dc.contributor.authorPeti, Wolfgang
dc.contributor.authorNilsson, Jakob
dc.contributor.authorPage, Rebecca
dc.date.accessioned2020-04-01T05:02:27Z
dc.date.available2020-04-01T05:02:27Z
dc.date.issued2020-03-20
dc.date.submitted2020-02-12
dc.identifier.other55966
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/303984
dc.description.abstractThe 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.
dc.languageen
dc.publishereLife Sciences Publications, Ltd
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectResearch Article
dc.subjectBiochemistry and Chemical Biology
dc.subjectStructural Biology and Molecular Biophysics
dc.subjectprotein phosphatase
dc.subjectPP2A-B56
dc.subjectintrinsically disordered protein
dc.subjectdynamic, charge-charge interactions
dc.subjectKIF4A
dc.subjectstructural and cell biology
dc.subjectE. coli
dc.subjectHuman
dc.titleA dynamic charge-charge interaction modulates PP2A:B56 substrate recruitment
dc.typeArticle
dc.date.updated2020-04-01T05:02:27Z
prism.publicationNameeLife
prism.volume9
dc.identifier.doi10.17863/CAM.51068
dcterms.dateAccepted2020-03-14
rioxxterms.versionofrecord10.7554/elife.55966
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
datacite.contributor.supervisoreditor: Hunter, Tony
datacite.contributor.supervisorsenior_editor: Ron, David
dc.contributor.orcidWang, Xinru [0000-0001-5994-707X]
dc.contributor.orcidNasa, Isha [0000-0001-7699-795X]
dc.contributor.orcidZhang, Gang [0000-0001-7697-7203]
dc.contributor.orcidKettenbach, Arminja N [0000-0003-3979-4576]
dc.contributor.orcidNilsson, Jakob [0000-0003-4100-1125]
dc.contributor.orcidPage, Rebecca [0000-0002-4645-1232]
dc.identifier.eissn2050-084X
pubs.funder-project-idNational Institute of General Medical Sciences (R35GM119455)
pubs.funder-project-idNational Institute of General Medical Sciences (P20GM113132)
pubs.funder-project-idNational Institute of General Medical Sciences (R01GM098482)
pubs.funder-project-idNational Institute of Neurological Disorders and Stroke (R01NS091336)
pubs.funder-project-idNational Institute of General Medical Sciences (R01GM134683)
pubs.funder-project-idNovo Nordisk (NNF14CC0001)
pubs.funder-project-idIndependent Research Fund Denmark (DFF-7016-00086)


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)