0000000000628574
AUTHOR
Wolfgang Meyerhof
A binary genetic approach to characterize TRPM5 cells in mice
International audience; Transient receptor potential channel subfamily M member 5 (TRPM5) is an important downstream signaling component in a subset of taste receptor cells making it a potential target for taste modulation. Interestingly, TRPM5 has been detected in extra-oral tissues; however, the function of extra-gustatory TRPM5-expressing cells is less well understood. To facilitate visualization and manipulation of TRPM5-expressing cells in mice, we generated a Cre knock-in TRPM5 allele by homologous recombination. We then used the novel TRPM5-IRES-Cre mouse strain to report TRPM5 expression by activating a tau GFP transgene. To confirm faithful coexpression of tau GFP and TRPM5 we gene…
Resolution of the X-ray structure of gurmarin: new insights into the molecular mechanism of sweet taste receptor inhibition
International audience
The Crystal Structure of Gurmarin, a Sweet Taste–Suppressing Protein: Identification of the Amino Acid Residues Essential for Inhibition
International audience; Gurmarin is a highly specific sweet-taste suppressing protein in rodents that is isolated from the Indian plant Gymnemasylvestre. Gurmarin consists of 35 amino acid residues containing three intramolecular disulfide bridges that form a cystine knot. Here, we report the crystal structure of gurmarin at a 1.45 Å resolution and compare it with previously reported NMR solution structures. The atomic structure at this resolution allowed us to identify a very flexible region consisting of hydrophobic residues. Some of these amino acid residues had been identified as a putative binding site for the rat sweet taste receptor in a previous study. By combining alanine-scanning …
The X-ray structure of gurmarin provide new insights into amino acid residues essential for inhibition of the rat sweet taste receptor
International audience; Gurmarin is a polypeptide isolated from the Indian plant Gymnema sylvestre, which specifically suppresses sweet taste in rodents without affecting responses to other basic taste stimuli, such as HCl, NaCl, and quinine. Although the exact mechanism of gurmarin inhibition is not known, it has been shown that gurmarin acts via the T1R2/T1R3 sweet taste receptor. The gurmarin molecule is made of 35 amino-acid residues and three intramolecular disulfide bridges. We report herein the 1.45 Å X-ray structure of gurmarin heterologously produced using the yeast Pichia pastoris. The structure revealed a typical knottin fold, which is compared with previously reported NMR soluti…