Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Cheron, Jean-Baptiste | ko |
dc.contributor.author | Soohoo, Amanda | ko |
dc.contributor.author | Wang, Yi | ko |
dc.contributor.author | Golebiowski, Jerome | ko |
dc.contributor.author | Antonczak, Serge | ko |
dc.contributor.author | Jiang, Peihua | ko |
dc.contributor.author | Fiorucci, Sebastien | ko |
dc.date.accessioned | 2019-09-10T08:14:41Z | - |
dc.date.available | 2019-09-10T08:14:41Z | - |
dc.date.created | 2019-07-01 | - |
dc.date.issued | 2019-06 | - |
dc.identifier.citation | Chemical Senses, v.44, no.5, pp.303 - 310 | - |
dc.identifier.issn | 0379-864X | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/10620 | - |
dc.description.abstract | Mammalian sensory systems detect sweet taste through the activation of a single heteromeric T1R2/T1R3 receptor belonging to class C G-protein-coupled receptors. Allosteric ligands are known to interact within the transmembrane domain, yet a complete view of receptor activation remains elusive. By combining site-directed mutagenesis with computational modeling, we investigate the structure and dynamics of the allosteric binding pocket of the T1R3 sweet-taste receptor in its apo form, and in the presence of an allosteric ligand, cyclamate. A novel positively charged residue at the extracellular loop 2 is shown to interact with the ligand. Molecular dynamics simulations capture significant differences in the behavior of a network of conserved residues with and without cyclamate, although they do not directly interact with the allosteric ligand. Structural models show that they adopt alternate conformations, associated with a conformational change in the transmembrane region. Site-directed mutagenesis confirms that these residues are unequivocally involved in the receptor function and the allosteric signaling mechanism of the sweet-taste receptor. Similar to a large portion of the transmembrane domain, they are highly conserved among mammals, suggesting an activation mechanism that is evolutionarily conserved. This work provides a structural basis for describing the dynamics of the receptor, and for the rational design of new sweet-taste modulators. © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. | - |
dc.language | English | - |
dc.publisher | Oxford University Press | - |
dc.title | Conserved Residues Control the T1R3-Specific Allosteric Signaling Pathway of the Mammalian Sweet-Taste Receptor | - |
dc.type | Article | - |
dc.identifier.doi | 10.1093/chemse/bjz015 | - |
dc.identifier.wosid | 000481420700003 | - |
dc.identifier.scopusid | 2-s2.0-85067268592 | - |
dc.type.local | Article(Overseas) | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.contributor.nonIdAuthor | Cheron, Jean-Baptiste | - |
dc.contributor.nonIdAuthor | Soohoo, Amanda | - |
dc.contributor.nonIdAuthor | Wang, Yi | - |
dc.contributor.nonIdAuthor | Antonczak, Serge | - |
dc.contributor.nonIdAuthor | Jiang, Peihua | - |
dc.contributor.nonIdAuthor | Fiorucci, Sebastien | - |
dc.identifier.citationVolume | 44 | - |
dc.identifier.citationNumber | 5 | - |
dc.identifier.citationStartPage | 303 | - |
dc.identifier.citationEndPage | 310 | - |
dc.identifier.citationTitle | Chemical Senses | - |
dc.type.journalArticle | Article | - |
dc.description.isOpenAccess | N | - |
dc.subject.keywordAuthor | allosteric binding site | - |
dc.subject.keywordAuthor | class C GPCR | - |
dc.subject.keywordAuthor | cyclamate | - |
dc.subject.keywordAuthor | mammalian | - |
dc.subject.keywordAuthor | sweet-taste receptor | - |
dc.subject.keywordAuthor | taste modulator | - |
dc.subject.keywordPlus | ACTIVATION MECHANISM | - |
dc.subject.keywordPlus | HEPTAHELICAL DOMAIN | - |
dc.subject.keywordPlus | MOLECULAR-MECHANISM | - |
dc.subject.keywordPlus | MODULATION | - |
dc.subject.keywordPlus | SERVER | - |
dc.subject.keywordPlus | T1R3 | - |
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