Poster Presentation 2014 International Biophysics Congress

The interaction of G-protein coupled receptors with a sweet tasting protein and other gustatory delights (#446)

Robert Healey 1 2 3 4 , Shiva Prasad 3 , Angela M. Finch 4 , Pall Thordarson 1 2
  1. School of Chemistry, The University of New South Wales, Sydney, NSW, Australia
  2. ARC Centre of Excellence in Coherent Bio-Nano Science and Technology, The University of New South Wales, Sydney, NSW, Australia
  3. Neptune Bio-Innovations, North Ryde, NSW, Australia
  4. School of Medical Sciences, The University of New South Wales, Sydney, NSW, Australia

G protein-coupled receptors (GPCRs) allow transmission of local and long distance signalling within the body. They are responsible for cellular recognition of the physical senses such as taste, olfaction and sight as well as signal transduction of hormones and neurotransmitters. Over 850 GPCRs have been identified in the human genome all of which share a common structural element of seven transmembrane lipophilic moieties.1

Class C GPCRs function as homo- or hetero-dimers and are characterized by possession of large N-terminal ligand binding domains which exhibit a venus fly trap binding module.2  The class C taste receptors T1Rs, function only as heterodimers – the umami taste is T1R1/T1R3 and the sweet taste is T1R2/T1R3.3  The venus fly trap module of T1R2/T1R3 contains the orthosteric ligand binding site for sugars. A variety of sweet-tasting molecules exist which share no common structural features with sugar, these activate the receptor by allosteric means.

Allosteric activation and modulation of taste receptors, including the sweet-taste receptor have been investigated. In-vitro cell-based assays were performed using HEK-293 cells stably expressing Ga15-Gust protein co-transfected with hT1R2 and hT1R3. Various binding and functional assays were performed using radiolabelled and fluorescent signals to track binding to and activation of the receptor. The effect of cyclodextrins on the activation of the receptor was investigated.

  1. Rosenbaum, D. M., Rasmussen, S. G. F. & Kobilka, B. K. The structure and function of G-protein-coupled receptors. Nature 459, 356–63 (2009).
  2. Kunishima, N. et al. Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor. Nature 407, 971–7 (2000).
  3. Nelson, G., Hoon, M. & Chandrashekar, J. Mammalian sweet taste receptors. Cell 106, 381–390 (2001).