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TitleStructural basis of odorant recognition by a mammalian class II odorant receptor.
Journal, issue, pagesSci Adv, Vol. 12, Issue 13, Page eaeb9026, Year 2026
Publish dateMar 27, 2026
AuthorsMinsu Gil / Chulwon Choi / Minseok Kim / Minsik Bae / Hajin Lee / Intae Choi / Wonpil Im / Hee-Jung Choi /
PubMed AbstractMammalian odorant receptors (ORs) sense diverse environmental chemicals, yet structural insights into odorant recognition by mammalian class II ORs remain limited. Here, we present the cryo-EM ...Mammalian odorant receptors (ORs) sense diverse environmental chemicals, yet structural insights into odorant recognition by mammalian class II ORs remain limited. Here, we present the cryo-EM structure of a native mammalian class II OR, mouse Olfr412, a human OR1D2 ortholog, bound to the odorant methyl--cinnamate and the G protein. The odorant-binding pocket of Olfr412 is located deeper within the transmembrane domain than that of the class I OR OR51E2 and is largely composed of poorly conserved hydrophobic residues, providing a structural basis for broad odorant recognition in class II ORs. Structural and molecular dynamics analyses suggest that the conserved Y plays a key role in odorant recognition and activation, functionally paralleling R in class I ORs and is further stabilized by intramolecular interaction with the conserved ECL2 residue E. Together, our findings uncover structural mechanisms underlying odorant recognition and activation in class II ORs.
External linksSci Adv / PubMed:41894497 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 3.46 Å
Structure data

EMDB-65619: Globally refined map of odorant-bound mouse class II odorant receptor G protein complex
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-65620: Receptor-focused map of odorant-bound mouse class II odorant receptor G protein complex
Method: EM (single particle) / Resolution: 3.46 Å

65621

9w45

EMDB-65621, PDB-9w45:
The structure of odorant-bound mouse class II odorant receptor-miniGs complex
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

PDB-1mbb:
OXIDOREDUCTASE

Source
  • homo sapiens (human)
  • lama glama (llama)
  • mus musculus (house mouse)
KeywordsMEMBRANE PROTEIN/IMMUNE SYSTEM / Odorant receptor / MEMBRANE PROTEIN / MEMBRANE PROTEIN-IMMUNE SYSTEM complex

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