Structural basis of voltage gating in a partially activated K+ channel
Abstract
To understand the process of voltage activation in Kv channels, we determined the cryo-EM structure of the Shaker channel ILT mutant (V369I, I372L, S376T), known to partially decouple the gating charge movement of the voltage sensing domain (VSD) and the opening of the pore domain (PD). The structure captures an intermediate state in which the VSD is only partially activated while the gate of the PD remains closed. Combined with computational modeling based on AlphaFold2 predictions and molecular dynamics simulations, we show that the VSD activation is transduced to the PD via a dynamic shift in the population equilibrium of the S4-S5 linker between two metastable positions, thereby providing the basis for electromechanical coupling between the two domains.
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BibTeX
@article{agrawal2026structural,
title = {{Structural basis of voltage gating in a partially activated K+ channel}},
author = {Richa Agrawal and Ramon Mendoza Uriarte and Bernardo I. Pinto-Anwandter and Trayder Thomas and Lydia Blachowicz and Young Hoon Koh and Francisco Bezanilla and Eduardo Perozo and Benoît Roux},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78089-5},
url = {https://www.nature.com/articles/s41467-026-78089-5},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Structural basis of voltage gating in a partially activated K+ channel
AU - Richa Agrawal
AU - Ramon Mendoza Uriarte
AU - Bernardo I. Pinto-Anwandter
AU - Trayder Thomas
AU - Lydia Blachowicz
AU - Young Hoon Koh
AU - Francisco Bezanilla
AU - Eduardo Perozo
AU - Benoît Roux
PY - 2026
DA - 2026/10/01
JO - Nature Communications
DO - 10.1038/s41467-026-78089-5
UR - https://www.nature.com/articles/s41467-026-78089-5
AB - To understand the process of voltage activation in Kv channels, we determined the cryo-EM structure of the Shaker channel ILT mutant (V369I, I372L, S376T), known to partially decouple the gating charge movement of the voltage sensing domain (VSD) and the opening of the pore domain (PD). The structure captures an intermediate state in which the VSD is only partially activated while the gate of the PD remains closed. Combined with computational modeling based on AlphaFold2 predictions and molecular dynamics simulations, we show that the VSD activation is transduced to the PD via a dynamic shift in the population equilibrium of the S4-S5 linker between two metastable positions, thereby providing the basis for electromechanical coupling between the two domains.
SN - 2041-1723
ER -