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dc.contributor.authorKumar, Ganesan Senthil
dc.contributor.authorChoy, Meng S
dc.contributor.authorKoveal, Dorothy M
dc.contributor.authorLorinsky, Michael K
dc.contributor.authorLyons, Scott P
dc.contributor.authorKettenbach, Arminja N
dc.contributor.authorPage, Rebecca
dc.contributor.authorPeti, Wolfgang
dc.date.accessioned2019-05-09T20:43:22Z
dc.date.available2019-05-09T20:43:22Z
dc.date.issued2018-11-01
dc.identifier.citationKumar, G. S., Choy, M. S., Koveal, D. M., Lorinsky, M. K., Lyons, S. P., Kettenbach, A. N., ... & Peti, W. (2018). Identification of the substrate recruitment mechanism of the muscle glycogen protein phosphatase 1 holoenzyme. Science advances, 4(11), eaau6044.en_US
dc.identifier.issn2375-2548
dc.identifier.pmid30443599
dc.identifier.doi10.1126/sciadv.aau6044
dc.identifier.urihttp://hdl.handle.net/10150/632224
dc.description.abstractGlycogen is the primary storage form of glucose. Glycogen synthesis and breakdown are tightly controlled by glycogen synthase (GYS) and phosphorylase, respectively. The enzyme responsible for dephosphorylating GYS and phosphorylase, which results in their activation (GYS) or inactivation (phosphorylase) to robustly stimulate glycogen synthesis, is protein phosphatase 1 (PP1). However, our understanding of how PP1 recruits these substrates is limited. Here, we show how PP1, together with its muscle glycogen-targeting (GM) regulatory subunit, recruits and selectively dephosphorylates its substrates. Our molecular data reveal that the GM carbohydrate binding module (GMCBM21), which is amino-terminal to the GM PP1 binding domain, has a dual function in directing PP1 substrate specificity: It either directly recruits substrates (i.e., GYS) or recruits them indirectly by localization (via glycogen for phosphorylase). Our data provide the molecular basis for PP1 regulation by GM and reveal how PP1-mediated dephosphorylation is driven by scaffolding-based substrate recruitment.en_US
dc.description.sponsorshipAmerican Diabetes Association Pathway to Stop Diabetes Grant [1-14-ACN-31, R35GM119455, R01GM098482]en_US
dc.language.isoenen_US
dc.publisherAMER ASSOC ADVANCEMENT SCIENCEen_US
dc.relation.urlhttps://advances.sciencemag.org/content/4/11/eaau6044en_US
dc.rightsCopyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.titleIdentification of the substrate recruitment mechanism of the muscle glycogen protein phosphatase 1 holoenzymeen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Dept Chem & Biochemen_US
dc.identifier.journalSCIENCE ADVANCESen_US
dc.description.noteOpen access journalen_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitleScience advances
refterms.dateFOA2019-05-09T20:43:23Z


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Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
Except where otherwise noted, this item's license is described as Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).