Open AccessMolecular basis of multistep voltage activation in plant two-pore channel 1
Author(s) -
Miles Sasha Dickinson,
Jinping Lu,
Meghna Gupta,
Irene Marten,
Rainer Hedrich,
Robert M. Stroud
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2110936119
Subject(s) - depolarization , biophysics , ion channel , chemistry , membrane potential , voltage gated ion channel , potassium channel , membrane , biochemistry , biology , receptor
Significance Despite decades of biophysical and structural research, little is understood about how voltage-gated ion channels (VGICs) activate during membrane depolarization, and less is known about how VGICs can be modulated by lipids and other ligands. We identify multiple functional states of the voltage- and Ca2+ -gated ion channel TPC1 fromArabidopsis thaliana (AtTPC1), which confers electrical excitability to the plant vacuole. Here, we show how a voltage-sensing domain (VSD) functions during electrical activation and the mechanism of inhibition by vacuolar Ca2+ . We show that the VSD undergoes large-scale, domain-wide structural changes during activation that involves Ca2+ -dependent in-membrane plane rotation, subsequent charge transfer, and a Ca2+ -dependent gate in the pore mouth that is allosterically coupled to the VSD.