The Molecular Receptive Ranges of Human TAS2R Bitter Taste Receptors

TLDR

Humans detect thousands of bitter compounds, yet only about 25 TAS2R bitter taste receptors have been identified, raising the question of how such a limited set can sense this vast chemical space. The study aimed to determine how many bitter compounds each of the 25 human TAS2R receptors can detect. Researchers expressed the 25 receptors in a heterologous system and screened them against 104 natural or synthetic bitter chemicals. They identified 13 cognate ligands for 5 orphan receptors and 64 new ligands for known receptors, found that receptor tuning ranges vary from narrow to broad, that three receptors together recognize roughly half of the tested compounds, and that some bitter molecules activate up to 15 receptors, indicating that detection breadth is linked to the receptors’ molecular receptive ranges.

Abstract

Humans perceive thousands of compounds as bitter. In sharp contrast, only ∼25 taste 2 receptors (TAS2R) bitter taste receptors have been identified, raising the question as to how the vast array of bitter compounds can be detected by such a limited number of sensors. To address this issue, we have challenged 25 human taste 2 receptors (hTAS2Rs) with 104 natural or synthetic bitter chemicals in a heterologous expression system. Thirteen cognate bitter compounds for 5 orphan receptors and 64 new compounds for previously identified receptors were discovered. Whereas some receptors recognized only few agonists, others displayed moderate or extreme tuning broadness. Thus, 3 hTAS2Rs together were able to detect ∼50% of the substances used. Conversely, though 63 bitter substances activated only 1–3 receptors, 19 compounds stimulated up to 15 hTAS2Rs. Our data suggest that the detection of the numerous bitter chemicals is related to the molecular receptive ranges of hTAS2Rs.