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Structural basis of odorant recognition by a human odorant receptor.
Billesbølle, Christian B; de March, Claire A; van der Velden, Wijnand J C; Ma, Ning; Tewari, Jeevan; Del Torrent, Claudia Llinas; Li, Linus; Faust, Bryan; Vaidehi, Nagarajan; Matsunami, Hiroaki; Manglik, Aashish.
Affiliation
  • Billesbølle CB; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA.
  • de March CA; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA.
  • van der Velden WJC; Institut de Chimie des Substances Naturelles, UPR2301 CNRS, Université Paris-Saclay, Gif-sur-Yvette, France.
  • Ma N; Department of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA, USA.
  • Tewari J; Department of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA, USA.
  • Del Torrent CL; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA.
  • Li L; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA.
  • Faust B; Laboratory of Computational Medicine, Biostatistics Unit, Faculty of Medicine, Universitat Autònoma Barcelona, Bellaterra, Barcelona, Spain.
  • Vaidehi N; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA.
  • Matsunami H; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA.
  • Manglik A; Department of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA, USA. NVaidehi@coh.org.
Nature ; 615(7953): 742-749, 2023 03.
Article in En | MEDLINE | ID: mdl-36922591
Our sense of smell enables us to navigate a vast space of chemically diverse odour molecules. This task is accomplished by the combinatorial activation of approximately 400 odorant G protein-coupled receptors encoded in the human genome1-3. How odorants are recognized by odorant receptors remains unclear. Here we provide mechanistic insight into how an odorant binds to a human odorant receptor. Using cryo-electron microscopy, we determined the structure of the active human odorant receptor OR51E2 bound to the fatty acid propionate. Propionate is bound within an occluded pocket in OR51E2 and makes specific contacts critical to receptor activation. Mutation of the odorant-binding pocket in OR51E2 alters the recognition spectrum for fatty acids of varying chain length, suggesting that odorant selectivity is controlled by tight packing interactions between an odorant and an odorant receptor. Molecular dynamics simulations demonstrate that propionate-induced conformational changes in extracellular loop 3 activate OR51E2. Together, our studies provide a high-resolution view of chemical recognition of an odorant by a vertebrate odorant receptor, providing insight into how this large family of G protein-coupled receptors enables our olfactory sense.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Propionates / Receptors, Odorant / Cryoelectron Microscopy / Odorants Limits: Humans Language: En Journal: Nature Year: 2023 Type: Article Affiliation country: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Propionates / Receptors, Odorant / Cryoelectron Microscopy / Odorants Limits: Humans Language: En Journal: Nature Year: 2023 Type: Article Affiliation country: United States