Phosphorylation of PPAR gamma Affects the Collective Motions of the PPAR gamma-RXR alpha-DNA Complex

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dc.contributor.authorLemkul, Justin A.en
dc.contributor.authorLewis, Stephanie N.en
dc.contributor.authorBassaganya-Riera, Josepen
dc.contributor.authorBevan, David R.en
dc.contributor.departmentBiochemistryen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.date.accessioned2016-12-23T14:38:50Zen
dc.date.available2016-12-23T14:38:50Zen
dc.date.issued2015-05-08en
dc.description.abstractPeroxisome-proliferator activated receptor-γ (PPARγ) is a nuclear hormone receptor that forms a heterodimeric complex with retinoid X receptor-α (RXRα) to regulate transcription of genes involved in fatty acid storage and glucose metabolism. PPARγ is a target for pharmaceutical intervention in type 2 diabetes, and insight into interactions between PPARγ, RXRα, and DNA is of interest in understanding the function and regulation of this complex. Phosphorylation of PPARγ by cyclin-dependent kinase 5 (Cdk5) has been shown to dysregulate the expression of metabolic regulation genes, an effect that is counteracted by PPARγ ligands. We applied molecular dynamics (MD) simulations to study the relationship between the ligand-binding domains of PPARγ and RXRα with their respective DNA-binding domains. Our results reveal that phosphorylation alters collective motions within the PPARγ-RXRα complex that affect the LBD-LBD dimerization interface and the AF-2 coactivator binding region of PPARγ.en
dc.description.sponsorshipVirginia Tech. College of Agriculture and Life Sciences. Biodesign and Bioprocessing Research Centeren
dc.description.sponsorshipVirginia Tech. Advanced Research Computingen
dc.description.sponsorshipNational Science Foundationen
dc.description.sponsorshipCNS-0960081en
dc.description.versionPublished versionen
dc.format.extent21 pagesen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationLemkul JA, Lewis SN, Bassaganya-Riera J, Bevan DR (2015) Phosphorylation of PPARγ Affects the Collective Motions of the PPARγ-RXRα-DNA Complex. PLoS ONE 10(5): e0123984. doi:10.1371/ journal.pone.0123984en
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0123984en
dc.identifier.issn1932-6203en
dc.identifier.issn1932-6203en
dc.identifier.issue5en
dc.identifier.urihttp://hdl.handle.net/10919/73812en
dc.identifier.volume10en
dc.language.isoenen
dc.publisherPLOSen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000356768100024&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectactivated receptor-gammaen
dc.subjectparticle mesh ewalden
dc.subjectmolecular simulationen
dc.subjectligand-bindingen
dc.subjectprotein structuresen
dc.subjectpartial agonistsen
dc.subjectforce-fielden
dc.subjectmechanismen
dc.subjectdynamicsen
dc.subjectmacromoleculesen
dc.titlePhosphorylation of PPAR gamma Affects the Collective Motions of the PPAR gamma-RXR alpha-DNA Complexen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Biochemistryen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Biocomplexity Instituteen
pubs.organisational-group/Virginia Tech/University Research Institutes/Biocomplexity Institute/Researchersen
pubs.organisational-group/Virginia Tech/University Research Institutes/Biocomplexity Institute/SelectedFaculty1en

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