BBC Russian
Svoboda | Graniru | BBC Russia | Golosameriki | Facebook
Do data resources managed by EMBL-EBI and our collaborators make a difference to your work?
If so, please take 10 minutes to fill in our survey, and help us make the case for why sustaining open data resources is critical for life sciences research.

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy.

Bitter taste receptor activation by cholesterol and an intracellular tastant.

Author information

Affiliations

  • 1. Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
      Authors
    • Kim Y 1
    • Gumpper RH 1
    • Liu Y 1
    • Kocak DD 1
    • Krumm BE 1
    • Jain MK 1
    • Zhang S 1
    • Roth BL 1
    (8 authors)
  • 2. Mount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences, Oncological Sciences and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
      Authors
    • Xiong Y 2
    • Deng Z 2
    • Jin J 2
    (3 authors)
  • 3. School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
      Authors
    • Cao C 3
    (1 author)

ORCIDs linked to this article

Show all (8)

Nature, 10 Apr 2024, 628(8008):664-671
https://doi.org/10.1038/s41586-024-07253-y PMID: 38600377 

Abstract 

Bitter taste sensing is mediated by type 2 taste receptors (TAS2Rs (also known as T2Rs)), which represent a distinct class of G-protein-coupled receptors1. Among the 26 members of the TAS2Rs, TAS2R14 is highly expressed in extraoral tissues and mediates the responses to more than 100 structurally diverse tastants2-6, although the molecular mechanisms for recognizing diverse chemicals and initiating cellular signalling are still poorly understood. Here we report two cryo-electron microscopy structures for TAS2R14 complexed with Ggust (also known as gustducin) and Gi1. Both structures have an orthosteric binding pocket occupied by endogenous cholesterol as well as an intracellular allosteric site bound by the bitter tastant cmpd28.1, including a direct interaction with the α5 helix of Ggust and Gi1. Computational and biochemical studies validate both ligand interactions. Our functional analysis identified cholesterol as an orthosteric agonist and the bitter tastant cmpd28.1 as a positive allosteric modulator with direct agonist activity at TAS2R14. Moreover, the orthosteric pocket is connected to the allosteric site via an elongated cavity, which has a hydrophobic core rich in aromatic residues. Our findings provide insights into the ligand recognition of bitter taste receptors and suggest activities of TAS2R14 beyond bitter taste perception via intracellular allosteric tastants.

Full text links 

Read article at publisher's site: https://doi.org/10.1038/s41586-024-07253-y

References 

Articles referenced by this article (61)

Show 10 more references (10 of 61)

Citations & impact 

This article has not been cited yet.

Impact metrics

2
Data citations
Jump to Data

Alternative metrics

Altmetric item for https://www.altmetric.com/details/162132544
Altmetric
Discover the attention surrounding your research
https://www.altmetric.com/details/162132544

Data 

Similar Articles 

To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.