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TitleThe structural basis of odorant recognition in insect olfactory receptors.
Journal, issue, pagesNature, Vol. 597, Issue 7874, Page 126-131, Year 2021
Publish dateAug 4, 2021
AuthorsJosefina Del Mármol / Mackenzie A Yedlin / Vanessa Ruta /
PubMed AbstractOlfactory systems must detect and discriminate amongst an enormous variety of odorants. To contend with this challenge, diverse species have converged on a common strategy in which odorant identity ...Olfactory systems must detect and discriminate amongst an enormous variety of odorants. To contend with this challenge, diverse species have converged on a common strategy in which odorant identity is encoded through the combinatorial activation of large families of olfactory receptors, thus allowing a finite number of receptors to detect a vast chemical world. Here we offer structural and mechanistic insight into how an individual olfactory receptor can flexibly recognize diverse odorants. We show that the olfactory receptor MhOR5 from the jumping bristletail Machilis hrabei assembles as a homotetrameric odorant-gated ion channel with broad chemical tuning. Using cryo-electron microscopy, we elucidated the structure of MhOR5 in multiple gating states, alone and in complex with two of its agonists-the odorant eugenol and the insect repellent DEET. Both ligands are recognized through distributed hydrophobic interactions within the same geometrically simple binding pocket located in the transmembrane region of each subunit, suggesting a structural logic for the promiscuous chemical sensitivity of this receptor. Mutation of individual residues lining the binding pocket predictably altered the sensitivity of MhOR5 to eugenol and DEET and broadly reconfigured the receptor's tuning. Together, our data support a model in which diverse odorants share the same structural determinants for binding, shedding light on the molecular recognition mechanisms that ultimately endow the olfactory system with its immense discriminatory capacity.
External linksNature / PubMed:34349260 / PubMed Central
MethodsEM (single particle)
Resolution2.9 - 3.3 Å
Structure data

23372

7lic

EMDB-23372: The structure of the insect olfactory receptor OR5 from Machilis hrabei.
PDB-7lic: The structure of the insect olfactory receptor OR5 from Machilis hrabei
Method: EM (single particle) / Resolution: 3.3 Å

23374

7lid

EMDB-23374: The structure of the insect olfactory receptor OR5 from Machilis hrabei in complex with eugenol.
PDB-7lid: The structure of the insect olfactory receptor OR5 from Machilis hrabei in complex with eugenol
Method: EM (single particle) / Resolution: 2.9 Å

23375

7lig

EMDB-23375: The structure of the insect olfactory receptor OR5 from Machilis hrabei in complex with DEET.
PDB-7lig: The structure of the insect olfactory receptor OR5 from Machilis hrabei in complex with DEET
Method: EM (single particle) / Resolution: 2.9 Å

Chemicals

ChemComp-EOL:
2-methoxy-4-(prop-2-en-1-yl)phenol

ChemComp-DE3:
N,N-diethyl-3-methylbenzamide

Source
  • machilis hrabei (insect)
KeywordsMEMBRANE PROTEIN / olfactory receptor / ion channel / eugenol / DEET

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