8F76

Human olfactory receptor OR51E2 bound to propionate in complex with miniGs399

Summary for 8F76

• Entry DOI: 10.2210/pdb8f76/pdb
• EMDB information: 28896
• Descriptor: Olfactory receptor 51E2, Nanobody 35, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, ... (6 entities in total)
• Functional Keywords: human olfactory receptor, g protein-coupled receptor, odorant-binding, sensory transduction, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 131442.05

Authors

Billesboelle, C.B.,Manglik, A. (deposition date: 2022-11-18, release date: 2023-03-22, Last modification date: 2024-11-06)

Primary citation

Billesbolle, C.B.,de March, C.A.,van der Velden, W.J.C.,Ma, N.,Tewari, J.,Del Torrent, C.L.,Li, L.,Faust, B.,Vaidehi, N.,Matsunami, H.,Manglik, A.
Structural basis of odorant recognition by a human odorant receptor.
Nature, 615:742-749, 2023

PubMed Abstract: 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 genome. 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.

PubMed: 36922591
DOI: 10.1038/s41586-023-05798-y

Experimental method

ELECTRON MICROSCOPY (3.1 Å)