Non-classical amine recognition evolved in a large clade of olfactory receptors

  1. Qian Li
  2. Yaw Tachie-Baffour
  3. Zhikai Liu
  4. Maude W Baldwin
  5. Andrew C Kruse
  6. Stephen D Liberles  Is a corresponding author
  1. Harvard Medical School, United States
  2. Harvard University, United States

Abstract

Biogenic amines are important signaling molecules, and the structural basis for their recognition by G Protein-Coupled Receptors (GPCRs) is well understood. Amines are also potent odors, with some activating olfactory trace amine-associated receptors (TAARs). Here, we report that teleost TAARs evolved a new way to recognize amines in a non-classical orientation. Chemical screens de-orphaned eleven zebrafish TAARs, with agonists including serotonin, histamine, tryptamine, 2-phenylethylamine, putrescine, and agmatine. Receptors from different clades contact ligands through aspartates on transmembrane α-helices III (canonical Asp3.32) or V (non-canonical Asp5.42), and diamine receptors contain both aspartates. Non-classical monoamine recognition evolved in two steps: an ancestral TAAR acquired Asp5.42, gaining diamine sensitivity, and subsequently lost Asp3.32. Through this transformation, the fish olfactory system dramatically expanded its capacity to detect amines, ecologically significant aquatic odors. The evolution of a second, alternative solution for amine detection by olfactory receptors highlights the tremendous structural versatility intrinsic to GPCRs.

Article and author information

Author details

  1. Qian Li

    Department of Cell Biology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Yaw Tachie-Baffour

    Department of Cell Biology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Zhikai Liu

    Department of Cell Biology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Maude W Baldwin

    Department of Organismic and Evolutionary Biology, Museum of Comparative Zoology, Harvard University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Andrew C Kruse

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Stephen D Liberles

    Department of Cell Biology, Harvard Medical School, Boston, United States
    For correspondence
    Stephen_liberles@hms.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Jeremy Nathans, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, United States

Publication history

  1. Received: July 29, 2015
  2. Accepted: October 28, 2015
  3. Accepted Manuscript published: October 31, 2015 (version 1)
  4. Version of Record published: December 14, 2015 (version 2)

Copyright

© 2015, Li et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Qian Li
  2. Yaw Tachie-Baffour
  3. Zhikai Liu
  4. Maude W Baldwin
  5. Andrew C Kruse
  6. Stephen D Liberles
(2015)
Non-classical amine recognition evolved in a large clade of olfactory receptors
eLife 4:e10441.
https://doi.org/10.7554/eLife.10441

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