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A molecular sensor for cholesterol in the human serotonin 1A receptor

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dc.contributor.author Kumar, G Aditya
dc.contributor.author Sarkar, Parijat
dc.contributor.author Stepniewski, Tomasz Maciej, 1988-
dc.contributor.author Jafurulla, Md
dc.contributor.author Singh, Shishu Pal
dc.contributor.author Selent, Jana
dc.contributor.author Chattopadhyay, Amitabha
dc.date.accessioned 2021-10-08T06:03:39Z
dc.date.available 2021-10-08T06:03:39Z
dc.date.issued 2021
dc.identifier.citation Kumar GA, Sarkar P, Stepniewski TM, Jafurulla M, Singh SP, Selent J, Chattopadhyay A. A molecular sensor for cholesterol in the human serotonin 1A receptor. Sci Adv. 2021;7(30):eabh2922. DOI: 10.1126/sciadv.abh2922
dc.identifier.issn 2375-2548
dc.identifier.uri http://hdl.handle.net/10230/48590
dc.description.abstract The function of several G protein-coupled receptors (GPCRs) exhibits cholesterol sensitivity. Cholesterol sensitivity of GPCRs could be attributed to specific sequence and structural features, such as the cholesterol recognition/interaction amino acid consensus (CRAC) motif, that facilitate their cholesterol-receptor interaction. In this work, we explored the molecular basis of cholesterol sensitivity exhibited by the serotonin1A receptor, the most studied GPCR in the context of cholesterol sensitivity, by generating mutants of key residues in CRAC motifs in transmembrane helix 2 (TM2) and TM5 of the receptor. Our results show that a lysine residue (K101) in one of the CRAC motifs is crucial for sensing altered membrane cholesterol levels. Insights from all-atom molecular dynamics simulations showed that cholesterol-sensitive functional states of the serotonin1A receptor are associated with reduced conformational dynamics of extracellular loops of the receptor. These results constitute one of the first reports on the molecular mechanism underlying cholesterol sensitivity of GPCRs.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher American Association for the Advancement of Science (AAAS)
dc.relation.ispartof Sci Adv. 2021;7(30):eabh2922
dc.rights © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC)
dc.rights.uri https://creativecommons.org/licenses/by-nc/4.0/
dc.title A molecular sensor for cholesterol in the human serotonin 1A receptor
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1126/sciadv.abh2922
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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