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Descending to inhibit: Antagonist-induced downward shift of VSD II in TPC2
1Division of Biophysics and Neurobiology, Department of Molecular and Cellular Physiology, National Institute for Physiological Sciences, Okazaki, Aichi, Japan; Department of Physiological Sciences, School of Life Science, The Graduate University for Advanced Studies (SOKENDAI), Hayama, Kanagawa, Japan.
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.
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