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-Structure paper
Title | Molecular basis of multistep voltage activation in plant two-pore channel 1. |
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Journal, issue, pages | Proc Natl Acad Sci U S A, Vol. 119, Issue 9, Year 2022 |
Publish date | Mar 1, 2022 |
Authors | Miles Sasha Dickinson / Jinping Lu / Meghna Gupta / Irene Marten / Rainer Hedrich / Robert M Stroud / |
PubMed Abstract | Voltage-gated ion channels confer excitability to biological membranes, initiating and propagating electrical signals across large distances on short timescales. Membrane excitation requires channels ...Voltage-gated ion channels confer excitability to biological membranes, initiating and propagating electrical signals across large distances on short timescales. Membrane excitation requires channels that respond to changes in electric field and couple the transmembrane voltage to gating of a central pore. To address the mechanism of this process in a voltage-gated ion channel, we determined structures of the plant two-pore channel 1 at different stages along its activation coordinate. These high-resolution structures of activation intermediates, when compared with the resting-state structure, portray a mechanism in which the voltage-sensing domain undergoes dilation and in-membrane plane rotation about the gating charge-bearing helix, followed by charge translocation across the charge transfer seal. These structures, in concert with patch-clamp electrophysiology, show that residues in the pore mouth sense inhibitory Ca and are allosterically coupled to the voltage sensor. These conformational changes provide insight into the mechanism of voltage-sensor domain activation in which activation occurs vectorially over a series of elementary steps. |
External links | Proc Natl Acad Sci U S A / PubMed:35210362 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.5 - 3.5 Å |
Structure data | EMDB-25798, PDB-7tbg: EMDB-25825, PDB-7tdd: EMDB-25826, PDB-7tde: EMDB-25827, PDB-7tdf: |
Chemicals | ChemComp-CA: ChemComp-NA: ChemComp-HOH: |
Source |
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Keywords | TRANSPORT PROTEIN / ion channel / vacuole / plant / voltage / VGIC / membrane protein / voltage activation |