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Major haplotypes of the human bitter taste receptor TAS2R41 encode functional receptors for chloramphenicol.

Abstract：

:A complete understanding of bitterness perception requires identification of cognate bitter substances for all human bitter taste receptors (TAS2Rs). However, so far, no agonists have been identified for five of the 25 TAS2Rs, i.e., TAS2R41, TAS2R42, TAS2R45, TAS2R48 and TAS2R60. Due to substantial genetic variability several haplotypes exist for most bitter receptor genes. For some of the deorphaned TAS2Rs, haplotypes have been identified coding for proteins with severely impaired or even lacking receptor function, proposing that the use of non-functional receptor variants in previous investigations accounted for the failure to identify cognate bitter agonists for the orphan TAS2Rs. In the present report we reasoned that at least one out of the major genetically encoded TAS2R variants is functional. Therefore, we expressed the major haplotypes of the five orphan TAS2Rs in our functional assay and challenged the cells with 106 bitter compounds. Chloramphenicol was identified as agonist for TAS2R41. Further studies revealed that TAS2R41 is a 'specialist' receptor highly selective for this antibiotic. None of the other TAS2R variants responded to any of the 106 compounds, suggesting that the use of non-functional variants does not explain the failure to identify cognate agonists for the other four TAS2Rs. Probably, these TAS2Rs are highly selective for bitter substances absent in our compound library.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Thalmann S,Behrens M,Meyerhof W

doi

10.1016/j.bbrc.2013.04.066

subject

Has Abstract

pub_date

2013-05-31 00:00:00

pages

267-73

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(13)00705-5

journal_volume

435

pub_type

杂志文章

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