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Smelling Sulfur: Copper and Silver Regulate the Response of Human Odorant Receptor OR2T11 to Low-Molecular-Weight Thiols.

Publication ,  Journal Article
Li, S; Ahmed, L; Zhang, R; Pan, Y; Matsunami, H; Burger, JL; Block, E; Batista, VS; Zhuang, H
Published in: J Am Chem Soc
October 12, 2016

Mammalian survival depends on ultrasensitive olfactory detection of volatile sulfur compounds, since these compounds can signal the presence of rancid food, O2 depleted atmospheres, and predators (through carnivore excretions). Skunks exploit this sensitivity with their noxious spray. In commerce, natural and liquefied gases are odorized with t-BuSH and EtSH, respectively, as warnings. The 100-million-fold difference in olfactory perception between structurally similar EtSH and EtOH has long puzzled those studying olfaction. Mammals detect thiols and other odorants using odorant receptors (ORs), members of the family of seven transmembrane G-protein-coupled receptors (GPCRs). Understanding the regulator cofactors and response of ORs is particularly challenging due to the lack of X-ray structural models. Here, we combine computational modeling and site-directed mutagenesis with saturation transfer difference (STD) NMR spectroscopy and measurements of the receptor response profiles. We find that human thiol receptor OR2T11 responds specifically to gas odorants t-BuSH and EtSH requiring ionic copper for its robust activation and that this role of copper is mimicked by ionic and nanoparticulate silver. While copper is both an essential nutrient for life and, in excess, a hallmark of various pathologies and neurodegenerative diseases, its involvement in human olfaction has not been previously demonstrated. When screened against a series of alcohols, thiols, sulfides, and metal-coordinating ligands, OR2T11 responds with enhancement by copper to the mouse semiochemical CH3SCH2SH and derivatives, to four-membered cyclic sulfide thietane and to one- to four-carbon straight- and branched-chain and five-carbon branched-chain thiols but not to longer chain thiols, suggesting compact receptor dimensions. Alcohols are unreactive.

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Published In

J Am Chem Soc

DOI

EISSN

1520-5126

Publication Date

October 12, 2016

Volume

138

Issue

40

Start / End Page

13281 / 13288

Location

United States

Related Subject Headings

  • General Chemistry
  • 40 Engineering
  • 34 Chemical sciences
  • 03 Chemical Sciences
 

Citation

APA
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ICMJE
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Li, S., Ahmed, L., Zhang, R., Pan, Y., Matsunami, H., Burger, J. L., … Zhuang, H. (2016). Smelling Sulfur: Copper and Silver Regulate the Response of Human Odorant Receptor OR2T11 to Low-Molecular-Weight Thiols. J Am Chem Soc, 138(40), 13281–13288. https://doi.org/10.1021/jacs.6b06983
Li, Shengju, Lucky Ahmed, Ruina Zhang, Yi Pan, Hiroaki Matsunami, Jessica L. Burger, Eric Block, Victor S. Batista, and Hanyi Zhuang. “Smelling Sulfur: Copper and Silver Regulate the Response of Human Odorant Receptor OR2T11 to Low-Molecular-Weight Thiols.J Am Chem Soc 138, no. 40 (October 12, 2016): 13281–88. https://doi.org/10.1021/jacs.6b06983.
Li S, Ahmed L, Zhang R, Pan Y, Matsunami H, Burger JL, et al. Smelling Sulfur: Copper and Silver Regulate the Response of Human Odorant Receptor OR2T11 to Low-Molecular-Weight Thiols. J Am Chem Soc. 2016 Oct 12;138(40):13281–8.
Li, Shengju, et al. “Smelling Sulfur: Copper and Silver Regulate the Response of Human Odorant Receptor OR2T11 to Low-Molecular-Weight Thiols.J Am Chem Soc, vol. 138, no. 40, Oct. 2016, pp. 13281–88. Pubmed, doi:10.1021/jacs.6b06983.
Li S, Ahmed L, Zhang R, Pan Y, Matsunami H, Burger JL, Block E, Batista VS, Zhuang H. Smelling Sulfur: Copper and Silver Regulate the Response of Human Odorant Receptor OR2T11 to Low-Molecular-Weight Thiols. J Am Chem Soc. 2016 Oct 12;138(40):13281–13288.
Journal cover image

Published In

J Am Chem Soc

DOI

EISSN

1520-5126

Publication Date

October 12, 2016

Volume

138

Issue

40

Start / End Page

13281 / 13288

Location

United States

Related Subject Headings

  • General Chemistry
  • 40 Engineering
  • 34 Chemical sciences
  • 03 Chemical Sciences