{Reference Type}: Journal Article
{Title}: Descending to inhibit: Antagonist-induced downward shift of VSD II in TPC2.
{Author}: Shimomura T;
{Journal}: Structure
{Volume}: 32
{Issue}: 8
{Year}: 2024 Aug 8
{Factor}: 5.871
{DOI}: 10.1016/j.str.2024.07.005
{Abstract}: In this issue of Structure, Chi et al.1 report structural and functional studies that reveal the inhibition mechanism of the lysosomal two-pore channel TPC2 by the antagonist SG-094, which is of interest for drug development. Antagonist binding induces the downward displacement of the voltage-sensor domain II (VSD II), which is accompanied by asymmetric conformational rearrangements of the entire channel.