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Convergent olfactory trace amine-associated receptors detect biogenic polyamines with distinct motifs via a conserved binding site
Biogenic amines activate G-protein-coupled receptors (GPCRs) in the central nervous system in vertebrate animals. Several biogenic amines, when excreted, stimulate trace amine-associated receptors (TAARs), a group of GPCRs in the main olfactory epithelium, and elicit innate behaviors. How TAARs reco...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546428/ https://www.ncbi.nlm.nih.gov/pubmed/34600890 http://dx.doi.org/10.1016/j.jbc.2021.101268 |
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author | Jia, Liang Li, Shengju Dai, Wenxuan Guo, Lingna Xu, Zhengrong Scott, Anne M. Zhang, Zhe Ren, Jianfeng Zhang, Qinghua Dexheimer, Thomas S. Chung-Davidson, Yu-Wen Neubig, Richard R. Li, Qian Li, Weiming |
author_facet | Jia, Liang Li, Shengju Dai, Wenxuan Guo, Lingna Xu, Zhengrong Scott, Anne M. Zhang, Zhe Ren, Jianfeng Zhang, Qinghua Dexheimer, Thomas S. Chung-Davidson, Yu-Wen Neubig, Richard R. Li, Qian Li, Weiming |
author_sort | Jia, Liang |
collection | PubMed |
description | Biogenic amines activate G-protein-coupled receptors (GPCRs) in the central nervous system in vertebrate animals. Several biogenic amines, when excreted, stimulate trace amine-associated receptors (TAARs), a group of GPCRs in the main olfactory epithelium, and elicit innate behaviors. How TAARs recognize amines with varying numbers of amino groups is largely unknown. We reasoned that a comparison between lamprey and mammalian olfactory TAARs, which are thought to have evolved independently but show convergent responses to polyamines, may reveal structural determinants of amine recognition. Here, we demonstrate that sea lamprey TAAR365 (sTAAR365) responds strongly to biogenic polyamines cadaverine, putrescine, and spermine, and shares a similar response profile as a mammalian TAAR (mTAAR9). Docking and site-directed mutagenesis analyses show that both sTAAR365 and mTAAR9 recognize the two amino groups of cadaverine with the conserved Asp(3.32) and Tyr(6.51) residues. sTAAR365, which has remarkable sensitivity for cadaverine (EC(50) = 4 nM), uses an extra residue, Thr(7.42), to stabilize ligand binding. These cadaverine recognition sites also interact with amines with four and three amino groups (spermine and spermidine, respectively). Glu(7.36) of sTAAR365 cooperates with Asp(3.32) and Thr(7.42) to recognize spermine, whereas mTAAR9 recognizes spermidine through an additional aromatic residue, Tyr(7.43). These results suggest a conserved mechanism whereby independently evolved TAAR receptors recognize amines with two, three, or four amino groups using the same recognition sites, at which sTAAR365 and mTAAR9 evolved distinct motifs. These motifs interact directly with the amino groups of the polyamines, a class of potent and ecologically important odorants, mediating olfactory signaling. |
format | Online Article Text |
id | pubmed-8546428 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-85464282021-10-29 Convergent olfactory trace amine-associated receptors detect biogenic polyamines with distinct motifs via a conserved binding site Jia, Liang Li, Shengju Dai, Wenxuan Guo, Lingna Xu, Zhengrong Scott, Anne M. Zhang, Zhe Ren, Jianfeng Zhang, Qinghua Dexheimer, Thomas S. Chung-Davidson, Yu-Wen Neubig, Richard R. Li, Qian Li, Weiming J Biol Chem Research Article Biogenic amines activate G-protein-coupled receptors (GPCRs) in the central nervous system in vertebrate animals. Several biogenic amines, when excreted, stimulate trace amine-associated receptors (TAARs), a group of GPCRs in the main olfactory epithelium, and elicit innate behaviors. How TAARs recognize amines with varying numbers of amino groups is largely unknown. We reasoned that a comparison between lamprey and mammalian olfactory TAARs, which are thought to have evolved independently but show convergent responses to polyamines, may reveal structural determinants of amine recognition. Here, we demonstrate that sea lamprey TAAR365 (sTAAR365) responds strongly to biogenic polyamines cadaverine, putrescine, and spermine, and shares a similar response profile as a mammalian TAAR (mTAAR9). Docking and site-directed mutagenesis analyses show that both sTAAR365 and mTAAR9 recognize the two amino groups of cadaverine with the conserved Asp(3.32) and Tyr(6.51) residues. sTAAR365, which has remarkable sensitivity for cadaverine (EC(50) = 4 nM), uses an extra residue, Thr(7.42), to stabilize ligand binding. These cadaverine recognition sites also interact with amines with four and three amino groups (spermine and spermidine, respectively). Glu(7.36) of sTAAR365 cooperates with Asp(3.32) and Thr(7.42) to recognize spermine, whereas mTAAR9 recognizes spermidine through an additional aromatic residue, Tyr(7.43). These results suggest a conserved mechanism whereby independently evolved TAAR receptors recognize amines with two, three, or four amino groups using the same recognition sites, at which sTAAR365 and mTAAR9 evolved distinct motifs. These motifs interact directly with the amino groups of the polyamines, a class of potent and ecologically important odorants, mediating olfactory signaling. American Society for Biochemistry and Molecular Biology 2021-09-30 /pmc/articles/PMC8546428/ /pubmed/34600890 http://dx.doi.org/10.1016/j.jbc.2021.101268 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Jia, Liang Li, Shengju Dai, Wenxuan Guo, Lingna Xu, Zhengrong Scott, Anne M. Zhang, Zhe Ren, Jianfeng Zhang, Qinghua Dexheimer, Thomas S. Chung-Davidson, Yu-Wen Neubig, Richard R. Li, Qian Li, Weiming Convergent olfactory trace amine-associated receptors detect biogenic polyamines with distinct motifs via a conserved binding site |
title | Convergent olfactory trace amine-associated receptors detect biogenic polyamines with distinct motifs via a conserved binding site |
title_full | Convergent olfactory trace amine-associated receptors detect biogenic polyamines with distinct motifs via a conserved binding site |
title_fullStr | Convergent olfactory trace amine-associated receptors detect biogenic polyamines with distinct motifs via a conserved binding site |
title_full_unstemmed | Convergent olfactory trace amine-associated receptors detect biogenic polyamines with distinct motifs via a conserved binding site |
title_short | Convergent olfactory trace amine-associated receptors detect biogenic polyamines with distinct motifs via a conserved binding site |
title_sort | convergent olfactory trace amine-associated receptors detect biogenic polyamines with distinct motifs via a conserved binding site |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546428/ https://www.ncbi.nlm.nih.gov/pubmed/34600890 http://dx.doi.org/10.1016/j.jbc.2021.101268 |
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