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Allosteric modulation of a human odorant receptor.
Trimmer, Casey; Arroyave, Randy; Vuilleumier, Christine; Wu, Lily; Dumer, Aleksey; DeLaura, Christie; Kim, Jehoon; Pierce, Georgia M; Borisovska, Maria; De Nanteuil, Florian; Emberger, Matthew; Varganov, Yakov; Margot, Christian; Rogers, Matthew E; Pfister, Patrick.
Affiliation
  • Trimmer C; Firmenich Inc., 250 Plainsboro Road, Plainsboro, NJ 08536, USA.
  • Arroyave R; Firmenich Inc., 250 Plainsboro Road, Plainsboro, NJ 08536, USA.
  • Vuilleumier C; Firmenich SA, 7 Rue de la Bergère, Satigny 1242, Switzerland.
  • Wu L; Firmenich Inc., 250 Plainsboro Road, Plainsboro, NJ 08536, USA.
  • Dumer A; Firmenich Inc., 250 Plainsboro Road, Plainsboro, NJ 08536, USA.
  • DeLaura C; Firmenich Inc., 250 Plainsboro Road, Plainsboro, NJ 08536, USA.
  • Kim J; Firmenich Inc., 250 Plainsboro Road, Plainsboro, NJ 08536, USA.
  • Pierce GM; Firmenich Inc., 250 Plainsboro Road, Plainsboro, NJ 08536, USA.
  • Borisovska M; Firmenich Inc., 250 Plainsboro Road, Plainsboro, NJ 08536, USA.
  • De Nanteuil F; Firmenich SA, 7 Rue de la Bergère, Satigny 1242, Switzerland.
  • Emberger M; Firmenich Inc., 250 Plainsboro Road, Plainsboro, NJ 08536, USA.
  • Varganov Y; Firmenich Inc., 250 Plainsboro Road, Plainsboro, NJ 08536, USA.
  • Margot C; Firmenich SA, 7 Rue de la Bergère, Satigny 1242, Switzerland.
  • Rogers ME; Firmenich Inc., 250 Plainsboro Road, Plainsboro, NJ 08536, USA.
  • Pfister P; Firmenich Inc., 250 Plainsboro Road, Plainsboro, NJ 08536, USA. Electronic address: patrick.pfister@firmenich.com.
Curr Biol ; 33(8): 1523-1534.e4, 2023 04 24.
Article in En | MEDLINE | ID: mdl-36977419
Odor perception is first determined by how the myriad of environmental volatiles are detected at the periphery of the olfactory system. The combinatorial activation of dedicated odorant receptors generates enough encoding power for the discrimination of tens of thousands of odorants. Recent studies have revealed that odorant receptors undergo widespread inhibitory modulation of their activity when presented with mixtures of odorants, a property likely required to maintain discrimination and ensure sparsity of the code for complex mixtures. Here, we establish the role of human OR5AN1 in the detection of musks and identify distinct odorants capable of enhancing its activity in binary mixtures. Chemical and pharmacological characterization indicate that specific α-ß unsaturated aliphatic aldehydes act as positive allosteric modulators. Sensory experiments show decreased odor detection threshold in humans, suggesting that allosteric modulation of odorant receptors is perceptually relevant and likely adds another layer of complexity to how odors are encoded in the peripheral olfactory system.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Receptors, Odorant / Olfactory Receptor Neurons / Olfactory Perception Limits: Humans Language: En Journal: Curr Biol Journal subject: BIOLOGIA Year: 2023 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Receptors, Odorant / Olfactory Receptor Neurons / Olfactory Perception Limits: Humans Language: En Journal: Curr Biol Journal subject: BIOLOGIA Year: 2023 Document type: Article Affiliation country: Country of publication: