Choi, Chulwon Bae, Jungnam Kim, Seonghan Lee, Seho Kang, Hyunook Kim, Jinuk Bang, Injin Kim, Kiheon Huh, Won-Ki Seok, Chaok Park, Hahnbeom Im, Wonpil Choi, Hee-Jung 2024-01-19T08:02:08Z 2024-01-19T08:02:08Z 2024-01-11 2023-12 2041-1723 https://pubs.kist.re.kr/handle/201004/113003 Structural and mechanistic studies on human odorant receptors (ORs), key in olfactory signaling, are challenging because of their low surface expression in heterologous cells. The recent structure of OR51E2 bound to propionate provided molecular insight into odorant recognition, but the lack of an inactive OR structure limited understanding of the activation mechanism of ORs upon odorant binding. Here, we determined the cryo-electron microscopy structures of consensus OR52 (OR52cs), a representative of the OR52 family, in the ligand-free (apo) and octanoate-bound states. The apo structure of OR52cs reveals a large opening between transmembrane helices (TMs) 5 and 6. A comparison between the apo and active structures of OR52cs demonstrates the inward and outward movements of the extracellular and intracellular segments of TM6, respectively. These results, combined with molecular dynamics simulations and signaling assays, shed light on the molecular mechanisms of odorant binding and activation of the OR52 family. Limited insight existed on human odorant receptors (ORs). Here, the authors present structures of consensus OR52 in its inactive and active forms, shedding light on the activation mechanism of the OR52 family. English Nature Publishing Group Understanding the molecular mechanisms of odorant binding and activation of the human OR52 family Article 10.1038/s41467-023-43983-9 1 Nature Communications, v.14, no.1 Nature Communications 14 1 Y scie scopus 001117708200019 2-s2.0-85178909327 Multidisciplinary Sciences Science & Technology - Other Topics Article GUI MEMBRANE-BUILDER CRYSTAL-STRUCTURE OLFACTORY RECEPTOR CRYO-EM INTRACELLULAR RETENTION FUNCTIONAL EXPRESSION STRUCTURAL BASIS PROTEIN DYNAMICS REFINEMENT