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dc.contributor.authorGrinthal, Alison Elizabeth
dc.contributor.authorGuidotti, Guido
dc.date.accessioned2013-09-13T19:00:11Z
dc.date.issued2005
dc.identifier.citationGrinthal, Alison, and Guido Guidotti. 2007. Bilayer mechanical properties regulate transmembrane helix mobility and enzymatic state of CD39. Biochemistry 46(1): 279-290.en_US
dc.identifier.issn0006-2960en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11028289
dc.description.abstractCD39 can exist in at least two distinct functional states depending on the presence and intact membrane integration of its two transmembrane helices. In native membranes, the transmembrane helices undergo dynamic rotational motions that are required for enzymatic activity and are regulated by substrate binding. In the present study we show that bilayer mechanical properties regulate conversion between the two enzymatic functional states by modulating transmembrane helix dynamics. Alteration of membrane properties by insertion of cone shaped or inverse cone shaped amphiphiles or by cholesterol removal switches CD39 to the same enzymatic state as does removing or solubilizing the transmembrane domains. The same membrane alterations increase the propensity of both transmembrane helices to rotate within the packed structure, resulting in a structure with greater mobility but not an altered primary conformation. Membrane alteration also abolishes the ability of substrate to stabilize the helices in their primary conformation, indicating a loss of coupling between substrate binding and transmembrane helix dynamics. Removal of either transmembrane helix mimics the effect of membrane alteration on the mobility and substrate sensitivity of the remaining helix, suggesting that the ends of the extracellular domain have intrinsic flexibility. We suggest that a mechanical bilayer property, potentially elasticity, regulates CD39 by altering the balance between stability and flexibility of its transmembrane helices and, in turn, of its active site.en_US
dc.description.sponsorshipMolecular and Cellular Biologyen_US
dc.language.isoen_USen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.isversionofhttp://dx.doi.org/10.1021/bi061052pen_US
dc.relation.hasversionhttp://www.pubmedcentral.nih.gov/picrender.fcgi?artid=2536646&blobtype=pdfen_US
dash.licenseMETA_ONLY
dc.subjectmechanicalen_US
dc.subjectbilayeren_US
dc.subjectNTPDaseen_US
dc.subjectCD39en_US
dc.subjecttransmembrane helicesen_US
dc.titleBilayer Mechanical Properties Regulate Transmembrane Helix Mobility and Enzymatic State of CD39en_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalBiochemistryen_US
dash.depositing.authorGuidotti, Guido
dash.embargo.until10000-01-01
dc.identifier.doi10.1021/bi061052p*
workflow.legacycommentsPre OAP; publisher requires authors seek written permission to post even manuscripts. Committing metadata-onlyen_US
dash.contributor.affiliatedGuidotti, Guido
dash.contributor.affiliatedGrinthal, Alison


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