#Expi293 membrane pro crystal structure full#

Structural characteristics of the sweet taste receptor

In this review, we critically examine the existing literature regarding the cell surface expression, signaling partners and evidence for STR signaling beyond the tongue and explore the implications of the polymorphic nature of this receptor.

This is mostly due to the current lack of molecular pharmacology tools-there are few cell lines available containing endogenous STR, heterologous expression systems have struggled to achieve robust cell surface trafficking, not all antibodies for STR subunits are carefully validated, signal transduction pathways are poorly defined, and the majority of STR ligands have either low potency, multiple targets, or both. However, there are surprisingly few rigorous mechanistic studies of STR signal transduction, particularly in extraoral tissues. This expression pattern has led to the hypothesis that the STR acts as a glucose sensor in these tissues and has thus generated interest in its potential as a therapeutic target. While typically recognized for its expression in all taste buds of the circumvallate papillae ], the STR has since been discovered in tissues outside the tongue, notably those involved in regulation of energy metabolism such as adipose tissue, endocrine cells of the gut and the β-islet cells of the pancreas ]. It was subsequently determined that the ‘true’ STR likely consisted of an obligate heterodimer comprising TAS1R2 and TAS1R3 (TAS1R2/R3) ], while the umami receptor was formed by a TAS1R1/R3 heterodimer ]. Shortly thereafter, studies of the well-documented genetic association of the Sac locus with sweet taste preference in mice resulted in the discovery of a third TAS1 GPCR, taste 1 receptor 3 (TAS1R3) ] note that the distantly related TAS2 receptors detect bitter substances ]. In 1999 ], two GPCRs were identified in taste buds as responding to either sweet or umami taste and were named taste 1 receptor 1 (TAS1R1) and taste 1 receptor 2 (TAS1R2), respectively. Although there has been evidence for a STR for a long time, its identity was only relatively recently confirmed ]. The sweet taste receptor (STR) is a G protein-coupled receptor (GPCR) responsible for the detection of different types of sweet molecules by the tongue. extracellular signal-regulated kinases 1 and 2.Finally, we provide recommendations on the reporting of reference sequence identification numbers to avoid incorrect attribution of wild-type to these biologically significant polymorphisms, which we argue may have led to some of the inconsistencies in the field. Critically, the influence of receptor polymorphisms (including those associated with sugar consumption) on the molecular pharmacology of the receptor remains hitherto unexplored.

#Expi293 membrane pro crystal structure full#

Not only are the mechanisms controlling and regulating the surface expression of the STR unclear, but also research into the full repertoire of signaling partners of the STR is at present inconclusive. We find that despite 20 years of research into the STR, the target remains frustratingly enigmatic. Then, from a molecular pharmacology perspective, we dissect the research surrounding the regulation of STR surface expression and signal transduction, in both oral and extraoral tissues, and discuss the potential for the exploitation of biased agonists for the STR. In this review, we briefly describe the structural characteristics and functional relevance of the STR. It is now known that many pharmacologically exploitable binding sites exist across the extracellular and transmembrane regions of both subunits of the STR, indicative of its potential amenability to pharmacotherapeutic modulation. Interest in the STR has steadily grown, especially since its discovery in extraoral tissues hints at a metabolic role for the receptor. Considered an obligate heterodimer, it consists of taste 1 receptor 2 and taste 1 receptor 3 subunits. The class C G protein-coupled sweet taste receptor (STR) is responsible for the perception of sweet-tasting molecules.