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dc.contributor.authorDuncan, Anna Len
dc.contributor.authorRuprecht, Jonathanen
dc.contributor.authorKunji, Edmunden
dc.contributor.authorRobinson, Alanen
dc.date.accessioned2018-03-23T13:44:19Z
dc.date.available2018-03-23T13:44:19Z
dc.date.issued2018-05en
dc.identifier.issn0005-2736
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/274286
dc.description.abstractCardiolipin in eukaryotes is found in the mitochondrial inner membrane, where it interacts with membrane proteins and, although not essential, is necessary for the optimal activity of a number of proteins. One of them is the mitochondrial ADP/ATP carrier, which imports ADP into the mitochondrion and exports ATP. In the crystal structures, cardiolipin is bound to three equivalent sites of the ADP/ATP carrier, but its role is unresolved. Conservation of residues at these cardiolipin binding sites across other members of the mitochondrial carrier superfamily indicates cardiolipin binding is likely to be important for the function of all mitochondrial carriers. Multiscale simulations were performed in a cardiolipin-containing membrane to investigate the dynamics of cardiolipin around the yeast and bovine ADP/ATP carriers in a lipid bilayer and the properties of the cardiolipin-binding sites. In coarse-grain simulations, cardiolipin molecules bound to the carriers for longer periods of time than phosphatidylcholine and phosphatidylethanolamine lipids—with timescales in the tens of microseconds. Three long-lived cardiolipin binding sites overlapped with those in the crystal structures of the carriers. Other shorter-lived cardiolipin interaction sites were identified in both membrane leaflets. However, the timescales of the interactions were of the same order as phosphatidylcholine and phosphatidylethanolamine, suggesting that these sites are not specific for cardiolipin binding. The calculation of lipid binding times and the overlap of the cardiolipin binding sites between the structures and simulations demonstrate the potential of multiscale simulations to investigate the dynamics and behavior of lipids interacting with membrane proteins.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectMitochondriaen
dc.subjectAnimalsen
dc.subjectCattleen
dc.subjectSaccharomyces cerevisiaeen
dc.subjectCardiolipinsen
dc.subjectMitochondrial ADP, ATP Translocasesen
dc.subjectSaccharomyces cerevisiae Proteinsen
dc.subjectBinding Sitesen
dc.subjectAmino Acid Sequenceen
dc.subjectConserved Sequenceen
dc.subjectProtein Bindingen
dc.subjectModels, Molecularen
dc.subjectMitochondrial Membranesen
dc.subjectProtein Interaction Domains and Motifsen
dc.subjectMolecular Dynamics Simulationen
dc.titleCardiolipin dynamics and binding to conserved residues in the mitochondrial ADP/ATP carrier.en
dc.typeArticle
prism.endingPage1045
prism.issueIdentifier5en
prism.publicationDate2018en
prism.publicationNameBiochimica et biophysica acta. Biomembranesen
prism.startingPage1035
prism.volume1860en
dc.identifier.doi10.17863/CAM.21410
dcterms.dateAccepted2018-01-19en
rioxxterms.versionofrecord10.1016/j.bbamem.2018.01.017en
rioxxterms.versionAM*
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2018-05en
dc.contributor.orcidDuncan, Anna L [0000-0001-9873-4552]
dc.contributor.orcidRuprecht, Jonathan [0000-0002-1838-7245]
dc.contributor.orcidKunji, Edmund [0000-0002-0610-4500]
dc.contributor.orcidRobinson, Alan [0000-0001-9943-0059]
dc.identifier.eissn1879-2642
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_U105674181)
pubs.funder-project-idMRC (MC_U105663139)
pubs.funder-project-idBBSRC (BB/R50564X/1)
pubs.funder-project-idMRC (MC_UU_00015/1)
rioxxterms.freetoread.startdate2019-01-31


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