%0 Journal Article
%T Descending to inhibit: Antagonist-induced downward shift of VSD II in TPC2.
%A Shimomura T
%J Structure
%V 32
%N 8
%D 2024 Aug 8
%M 39121835
%F 5.871
%R 10.1016/j.str.2024.07.005
%X 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.