1.A.4.4.1
Vacuolar, voltage-dependent cation-selective, Ca²⁺-activated channel, YVC1. (Yeast vacuolar conductance protein 1; also called TrpY1; Yor088w) (Chang et al., 2009). Activated by stretch to release vacuolar Ca²⁺ into the cytoplasm upon osmotic upshock (Zhou et al. 2005). (Also activated by glucose, indole and other aromatic compounds (Haynes et al., 2008; Groppi et al. 2011)).  Glutathione activates by reversible glutathionylation of specific cysteyl residues in YVC1 (Chandel et al. 2016). Channel activity is activated by cytoplasmic Ca²⁺ and inhibited by vacuolar lumen Ca²⁺, and two residues, D401 and D405, are involved in Ca²⁺ sensing in the lumen (Amini et al. 2018). The cryoEM structure of TRPY1 at 3.1 Å resolution in a closed state has been determined (Ahmed et al. 2021). The structure, despite containing an evolutionarily conserved and archetypical transmembrane domain, reveals distinctive structural folds for the cytosolic N and C termini compared with other eukaryotic TRP channels. An inhibitory phosphatidylinositol 3-phosphate (PI(3)P) lipid-binding site, along with two Ca²⁺-binding sites were identified: a cytosolic site, implicated in channel activation, and a vacuolar lumen site, implicated in inhibition. TRPY1 channel modulation by lipids and Ca²⁺ have been revealed, and the molecular evolution of TRP channels has been suggested (Ahmed et al. 2021).