期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 78, 期 23, 页码 7605-7615出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-021-03968-7
关键词
Bitter taste receptor; GPCR; Structure-function relationships; Integrative structural biology
资金
- French Ministry of Higher Education and Research
- National Research Foundation of Korea (NRF) [NRF2020R1A2C2004661]
- GIRACT (Geneva, Switzerland)
- Gen Foundation
- French government through the UCAJEDI Investments in the Future project [ANR-15-IDEX-01]
Bitter taste receptors (TAS2Rs) are a poorly understood subgroup of G protein-coupled receptors (GPCRs), with their experimental structure yet to be determined and key-residues controlling their function mostly unknown. Researchers designed an integrative approach to improve comparative modeling of TAS2Rs.
Bitter taste receptors (TAS2Rs) are a poorly understood subgroup of G protein-coupled receptors (GPCRs). The experimental structure of these receptors has yet to be determined, and key-residues controlling their function remain mostly unknown. We designed an integrative approach to improve comparative modeling of TAS2Rs. Using current knowledge on class A GPCRs and existing experimental data in the literature as constraints, we pinpointed conserved motifs to entirely re-align the amino-acid sequences of TAS2Rs. We constructed accurate homology models of human TAS2Rs. As a test case, we examined the accuracy of the TAS2R16 model with site-directed mutagenesis and in vitro functional assays. This combination of in silico and in vitro results clarifies sequence-function relationships and proposes functional molecular switches that encode agonist sensing and downstream signaling mechanisms within mammalian TAS2Rs sequences.
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