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dc.contributor.authorGarcia, Galo
dc.contributor.authorChiara, David C
dc.contributor.authorNirthanan, Selvanayagam
dc.contributor.authorHamouda, Ayman K
dc.contributor.authorStewart, Deirdre S
dc.contributor.authorCohen, Jonathan B
dc.date.accessioned2017-05-03T15:28:59Z
dc.date.available2017-05-03T15:28:59Z
dc.date.issued2007
dc.date.modified2014-10-08T01:42:40Z
dc.identifier.issn0006-2960
dc.identifier.doi10.1021/bi7008163
dc.identifier.urihttp://hdl.handle.net/10072/25827
dc.description.abstractInteractions of benzophenone (BP) with the Torpedo nicotinic acetylcholine receptor (nAChR) were characterized by electrophysiological analyses, radioligand binding assays, and photolabeling of nAChR-rich membranes with [3H]BP to identify the amino acids contributing to its binding sites. BP acted as a low potency noncompetitive antagonist, reversibly inhibiting the ACh responses of nAChRs expressed in Xenopus oocytes (IC50 = 600 卩 and the binding of the noncompetitive antagonist [3H]tetracaine to nAChR-rich membranes (IC50 = 150 卩. UV irradiation at 365 nm resulted in covalent incorporation of [3H]BP into the nAChR subunits (d > a ߠ> ?), with photoincorporation limited to the nAChR transmembrane domain. Comparison of nAChR photolabeling in the closed state (absence of agonist) and desensitized state (equilibrated with agonist) revealed selective desensitized state labeling in the d subunit of dPhe-232 in dM1 and dPro-286/dIle-288 near the beginning of dM3 that are within a pocket at the interface between the transmembrane and extracellular domains. There was labeling in the closed state within the ion channel at position M2-13 (aVal-255, ߖal-261, and dVal-269) that was reduced by 90% upon desensitization and labeling in the transmembrane M3 helices of the ߠand ? subunits (ߍet-285, ߍet-288, and ?Met-291) that was reduced by 50-80% in the desensitized state. Labeling at the lipid interface (aMet-415 in aM4) was unaffected by agonist. These results provide a further definition of the regions in the nAChR transmembrane domain that differ in structure between the closed and desensitized states.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoen_US
dc.publisherAmerican Chemical Society
dc.publisher.placeWashington, DC
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom10296
dc.relation.ispartofpageto10307
dc.relation.ispartofissue36
dc.relation.ispartofjournalBiochemistry
dc.relation.ispartofvolume46
dc.rights.retentionY
dc.subject.fieldofresearchBiochemistry and Cell Biology not elsewhere classified
dc.subject.fieldofresearchReceptors and Membrane Biology
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchMedical Biochemistry and Metabolomics
dc.subject.fieldofresearchMedicinal and Biomolecular Chemistry
dc.subject.fieldofresearchcode060199
dc.subject.fieldofresearchcode060110
dc.subject.fieldofresearchcode0601
dc.subject.fieldofresearchcode1101
dc.subject.fieldofresearchcode0304
dc.title3H]Benzophenone Photolabeling Identifies State-Dependent Changes in Nicotinic Acetylcholine Receptor Structure
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2007
gro.hasfulltextNo Full Text
gro.griffith.authorNirthanan, Niru


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