Characterization of an open-channel structure and lateral conduction pathway in the cation-selective pentameric ligand-gated ion channel, ELIC
Abstract
Open-channel structures of multiple pentameric ligand-gated ion channels (pLGICs) have been determined, including the prokaryotic model pLGIC, Erwinia ligand-gated ion channel (ELIC). For many of these structures, it remains uncertain whether they represent a physiologic open-channel state because the conditions used for structure determination do not match those of functional measurements in cell membranes. Here, MD simulation is used to examine the ion conduction properties of the ELIC open-channel structure, which was determined using a non-desensitizing mutant called ELIC5. Results from simulations show that the pore remains stably open on the microsecond timescale, but computational electrophysiology measurements demonstrate a large outward rectification and an inward conductance that is significantly lower than experiment. This discrepancy is attributed to a constricted extracellular domain (ECD), which restricts the passage of ions between the ECD vestibule and extracellular solution. Unbiased MD simulation of the ELIC5 structure demonstrates spontaneous widening of an intersubunit space in the ECD to expose a lateral fenestration, which becomes the dominant ion conduction pathway. Computational electrophysiology of the ELIC5 MD-refined structures with a widened lateral fenestration shows better agreement with experimental single-channel recordings. Mutations of residues along the lateral ion conduction pathway show reduced single-channel conductance, supporting the importance of the lateral fenestration for ion conduction in a cation-selective pLGIC.
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BibTeX
@article{arcario2026characterization,
title = {{Characterization of an open-channel structure and lateral conduction pathway in the cation-selective pentameric ligand-gated ion channel, ELIC}},
author = {Mark J Arcario and Elizabeth J Wu-Chen and Yuna Shim and Jérôme Hénin and Grace Brannigan and Wayland W.L. Cheng},
journal = {Journal of General Physiology},
year = {2026},
month = aug,
doi = {10.1085/jgp.202513926},
url = {https://hal.science/hal-05733293v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Characterization of an open-channel structure and lateral conduction pathway in the cation-selective pentameric ligand-gated ion channel, ELIC
AU - Mark J Arcario
AU - Elizabeth J Wu-Chen
AU - Yuna Shim
AU - Jérôme Hénin
AU - Grace Brannigan
AU - Wayland W.L. Cheng
PY - 2026
DA - 2026/08/27
JO - Journal of General Physiology
DO - 10.1085/jgp.202513926
UR - https://hal.science/hal-05733293v1
AB - Open-channel structures of multiple pentameric ligand-gated ion channels (pLGICs) have been determined, including the prokaryotic model pLGIC, Erwinia ligand-gated ion channel (ELIC). For many of these structures, it remains uncertain whether they represent a physiologic open-channel state because the conditions used for structure determination do not match those of functional measurements in cell membranes. Here, MD simulation is used to examine the ion conduction properties of the ELIC open-channel structure, which was determined using a non-desensitizing mutant called ELIC5. Results from simulations show that the pore remains stably open on the microsecond timescale, but computational electrophysiology measurements demonstrate a large outward rectification and an inward conductance that is significantly lower than experiment. This discrepancy is attributed to a constricted extracellular domain (ECD), which restricts the passage of ions between the ECD vestibule and extracellular solution. Unbiased MD simulation of the ELIC5 structure demonstrates spontaneous widening of an intersubunit space in the ECD to expose a lateral fenestration, which becomes the dominant ion conduction pathway. Computational electrophysiology of the ELIC5 MD-refined structures with a widened lateral fenestration shows better agreement with experimental single-channel recordings. Mutations of residues along the lateral ion conduction pathway show reduced single-channel conductance, supporting the importance of the lateral fenestration for ion conduction in a cation-selective pLGIC.
SN - 0022-1295
SN - 1540-7748
ER -