The Molecular Mechanisms of Bitter Taste

University courses Biological & Life Sciences
1

Microscopy structures unveil the mechanism underlying bitter taste perception

Recent cryo-electron microscopy (cryo-EM) studies on a human taste receptor have provided insights into the mechanisms responsible for our ability to detect bitter flavours.

Bad_taste__1602642358_10524
Bad_taste__1602642358_10524800×533 47.5 KB

The perception of bitter tastes is intricately linked to interactions between more than 100 compounds and a group of 26 receptors known as type-2 taste receptors (TAS2Rs). However, a lack of structural data has hindered our understanding of these interactions.

Researchers from the US and China have now presented two cryo-EM structures of the human bitter taste receptor TAS2R14. This receptor is distributed across cell membranes in the tongue and various other human tissues, capable of recognising and binding to over 100 structurally diverse compounds associated with bitter flavours.

The newly revealed structures highlight the presence of two binding sites on the receptor: an allosteric site situated within the cell and an orthosteric site located on the extracellular part of the receptor. Notably, a hydrophobic amino-acid residue-surrounded tunnel connects these two sites.

In terms of the receptor’s structure, the researchers observed cholesterol occupying the orthosteric site, a compound commonly found in animal cell membranes. This finding suggests that the receptor may exist in a semi-active state, primed for activation by bitter compounds. Additionally, the similarity in chemical structure between cholesterol and bile acids raises the possibility of bile acids also binding to and activating TAS2R14.

533537_41586_2024_7253_fig3_htmlcopy_18242

Comparison with TAS2R46, the only other TAS2R structure previously elucidated, revealed distinct structural variations in TAS2R14. This indicates that different TAS2R2 receptors may have specific binding affinities for particular types of molecules.

Furthermore, the researchers noted that TAS2R14 is expressed in numerous tissue types, with concentrations in the cerebellum surpassing those on the tongue by 100 times. Future investigations aim to uncover the receptor’s role in cellular signalling beyond oral taste perception.

Read the full article here:
https://www.nature.com/articles/s41586-024-07253-y

3 Likes
2

Whoa, I never knew there was so much science behind why we taste bitter stuff!

2 Likes
3

This is super fascinating! Do you think this might lead to new therapeutic interventions or treatments?

1 Like
4

These findings do open doors for new treatments! Understanding how bitter compounds interact with TAS2R14 could lead to:

  1. Drug Development: Designing molecules to modulate taste perception, improving medication taste.
  2. Obesity and Nutrition: Manipulating taste receptors to influence dietary choices and aid in weight management.
  3. Healthier Food Development: Developing food products that reduce the need for added sugars or artificial flavour enhancers.
  4. Treatment of Bitter Taste Disorders: Targeted therapies for individuals hypersensitive to bitter tastes.
  5. Exploring Beyond Taste Perception: Investigating TAS2R14’s roles in tissues beyond the tongue for potential therapeutic targets in neurological or metabolic disorders.
1 Like
5

Omg, this is so cool then! Healthier food development definitely sounds promising

1 Like