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TitleUnderstanding the molecular mechanisms of odorant binding and activation of the human OR52 family.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 8105, Year 2023
Publish dateDec 7, 2023
AuthorsChulwon Choi / Jungnam Bae / Seonghan Kim / Seho Lee / Hyunook Kang / Jinuk Kim / Injin Bang / Kiheon Kim / Won-Ki Huh / Chaok Seok / Hahnbeom Park / Wonpil Im / Hee-Jung Choi /
PubMed AbstractStructural 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 ...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), a representative of the OR52 family, in the ligand-free (apo) and octanoate-bound states. The apo structure of OR52 reveals a large opening between transmembrane helices (TMs) 5 and 6. A comparison between the apo and active structures of OR52 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.
External linksNat Commun / PubMed:38062020 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.84 - 3.66 Å
Structure data

EMDB-35010, PDB-8hti:
Human Consensus Olfactory Receptor OR52c in Complex with Octanoic Acid (OCA) and G Protein
Method: EM (single particle) / Resolution: 2.97 Å

EMDB-35770: Human Consensus Olfactory Receptor OR52c in Complex with Octanoic Acid (OCA) and G Protein (Consensus map)
Method: EM (single particle) / Resolution: 2.97 Å

EMDB-35772: Human Consensus Olfactory Receptor OR52c in Complex with Octanoic Acid (OCA) and G Protein (Receptor-focused map)
Method: EM (single particle) / Resolution: 3.09 Å

EMDB-35773: Human Consensus Olfactory Receptor OR52c in Complex with Octanoic Acid (OCA) and G Protein (G protein-focused map)
Method: EM (single particle) / Resolution: 2.84 Å

EMDB-35971, PDB-8j46:
Human Consensus Olfactory Receptor OR52c in apo state, OR52c-bRIL
Method: EM (single particle) / Resolution: 3.66 Å

EMDB-37336, PDB-8w77:
Human Consensus Olfactory Receptor OR52c in apo state, OR52c only
Method: EM (single particle) / Resolution: 3.61 Å

PDB-8htg:
Crystal structure of Golf in complex with GTP-gamma S and Mg
Method: X-RAY DIFFRACTION / Resolution: 2.91 Å

Chemicals

ChemComp-EDO:
1,2-ETHANEDIOL / Ethylene glycol

ChemComp-MG:
Unknown entry

ChemComp-GSP:
5'-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE

ChemComp-PO4:
PHOSPHATE ION / Phosphate

ChemComp-HOH:
WATER / Water

ChemComp-OCA:
OCTANOIC ACID (CAPRYLIC ACID) / Caprylic acid

Source
  • homo sapiens (human)
  • lama glama (llama)
  • mus musculus (house mouse)
  • escherichia coli (E. coli)
KeywordsSIGNALING PROTEIN / G protein / MEMBRANE PROTEIN / Olfactory Receptor / GPCR / Olfactory GPCR

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