The structure and function of taste G protein-coupled receptors and their implications in diseases

Taste G protein-coupled receptors (GPCRs), including sweet (TAS1Rs) and bitter (TAS2Rs) taste receptors, are essential for detecting nutrients and avoiding toxins, influencing dietary behavior, metabolism, and overall health. Beyond their role in taste perception, these receptors are widely expressed in extra-gustatory tissues, including the respiratory and gastrointestinal systems, where they regulate innate immune responses, hormone secretion, and energy balance. Dysfunctions or polymorphisms in TAS1Rs and TAS2Rs have been linked to various diseases such as asthma, type 2 diabetes, obesity, dental caries, periodontitis, and certain cancers. The structural features of these receptors, including their ligand-binding domains and signaling pathways, are central to their diverse functions. Recent studies also highlight their potential as therapeutic targets for managing conditions like metabolic syndrome and immune-related disorders. This review provides a detailed examination of the structural and functional dynamics of TAS1Rs and TAS2Rs, emphasizing their roles in disease mechanisms and exploring therapeutic strategies. While challenges remain in structural resolution and functional characterization, advancements in molecular modeling and pharmacological approaches shed light on their clinical potential. Understanding the tissue-specific roles and molecular mechanisms of taste GPCRs can pave the way for innovative treatments targeting these receptors, offering significant promise in addressing a range of health conditions.