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Zebrafish olfactory receptors ORAs differentially detect bile acids and bile salts

Title
Zebrafish olfactory receptors ORAs differentially detect bile acids and bile salts
Authors
Cong, XiaojingZheng, QianRen, WenwenCheron, Jean-BaptisteFiorucci, SebastienWen, TieqiaoZhang, ChunboYu, HongmengGolebiowski, JeromeYu, Yiqun
Issue Date
2019-04
Citation
Journal of Biological Chemistry, 294(17), 6762-6771
Type
Article
Article Type
Article
Author Keyword
site-directed mutagenesis; receptor structure-function; molecular docking; molecular dynamics; homology modeling; behavioral assay; fish ORA; olfactory receptor
Keyword
Biochemistry; Fish; Life cycle; Mammals; Pattern recognition; Salts; Chemosensory receptors; Heterologous cells; Ligand recognition; Lithocholic acids; Olfactory receptors; Olfactory systems; Site directed mutagenesis; Structure-function relationship; Body fluids
ISSN
0021-9258
Abstract
The fish olfactory receptor ORA family is orthologous to the mammalian vomeronasal receptors type 1. It consists of six highly conserved chemosensory receptors expected to be essential for survival and communication. We deorphanized the zebrafish ORA family in a heterologous cell system. The six receptors responded specifically to lithocholic acid (LCA) and closely related C24 5β-bile acids/salts. LCA attracted zebrafish as strongly as food in behavioral tests, whereas the less potent cholanic acid elicited weaker attraction, consistent with the in vitro results. The ORA-ligand recognition patterns were probed with site-directed mutagenesis guided by in silico modeling.We revealed the receptors' structure-function relationship underlying their specificity and selectivity for these compounds. Bile acids/salts are putative fish semiochemicals or pheromones sensed by the olfactory system with high specificity. This work identified their receptors and provided the basis for probing the roles of ORAs and bile acids/salts in fish chemosensation. © 2019 Cong et al.
URI
http://hdl.handle.net/20.500.11750/9857
DOI
10.1074/jbc.RA118.006483
Publisher
American Society for Biochemistry and Molecular Biology Inc.
Files:
There are no files associated with this item.
Collection:
ETC1. Journal Articles


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