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Nat. Commun., 07 December 2023 | https://doi.org/10.1038/s41467-023-43983-9 Understanding the molecular mechanisms of odorant binding and activation of the human OR52 family

Chulwon Choi ^1,7, Jungnam Bae ^1,7, Seonghan Kim ², Seho Lee ³, Hyunook Kang ¹, Jinuk Kim ¹, Injin Bang ^1,6, Kiheon Kim ¹, Won-Ki Huh ¹, Chaok Seok ³, Hahnbeom Park ⁴, Wonpil Im ^2,5 & Hee-Jung Choi ^1,*

¹Department of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea.
²Department of Bioengineering, Lehigh University, Bethlehem, PA 18015, USA.
³Department of Chemistry, Seoul National University, Seoul 08826, Republic of Korea.
⁴Brain Science Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
⁵Departments of Biological Sciences, Chemistry, and Computer Science and Engineering, Lehigh University, Bethlehem, PA 18015, USA.
⁶Present address: Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA.
⁷These authors contributed equally: Chulwon Choi, Jungnam Bae.

^*Corresponding authors: correspondence to Hee-Jung Choi

Abstract

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 (OR52_cs), a representative of the OR52 family, in the ligand-free (apo) and octanoate-bound states. The apo structure of OR52_cs reveals a large opening between transmembrane helices (TMs) 5 and 6. A comparison between the apo and active structures of OR52_cs 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.

논문정보

형식Research article
게재일2023년 12월 (BRIC 등록일 2023-12-08)
연구진국내(교신)+국외 연구진
분야 생명과학 > 구조생물 및 생물물리학

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