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Title: Ion Selectivity Mechanism in a Bacterial Pentameric Ligand-Gated Ion Channel

Abstract

The proton-gated ion channel from Gloeobacter violaceus (GLIC) is a prokaryotic homolog of the eukaryotic nicotinic acetylcholine receptor (nAChR) that responds to the binding of neurotransmitter acetylcholine and mediates fast signal transmission. Recent emergence of a high resolution crystal structure of GLIC captured in a potentially open state allowed detailed, atomic-level insight into ion conduction and selectivity mechanisms in these channels. Herein, we have examined the barriers to ion conduction and origins of ion selectivity in the GLIC channel by the construction of potential of mean force (PMF) profiles for sodium and chloride ions inside the transmembrane region. Our calculations reveal that the GLIC channel is open for a sodium ion to transport, but presents a ~10 kcal/mol free energy barrier for a chloride ion, which arises primarily from the unfavorable interactions with a ring of negatively charged glutamate residues (E-2 ) at the intracellular end and a ring of hydrophobic residues (I9 ) in the middle of the transmembrane domain. Our collective findings further suggest that the charge selection mechanism can, to a large extent, be attributed to the narrow intracellular end and a ring of glutamate residues in this position their strong negative electrostatics and ability to bindmore » cations. By contrast, E19 at the extracellular entrance only plays a minor role in ion selectivity of GLIC. In addition to electrostatics, both ion hydration and protein dynamics are found to be crucial for ion conduction as well, which explains why a chloride ion experiences a much greater barrier than a sodium ion in the hydrophobic region of the pore.« less

Authors:
 [1];  [1];  [2];  [1]
  1. ORNL
  2. Mayo Clinic College of Medicine
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Center for Computational Sciences
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1042763
DOE Contract Number:  
DE-AC05-00OR22725
Resource Type:
Journal Article
Journal Name:
Journal of the American Chemical Society
Additional Journal Information:
Journal Volume: 100; Journal Issue: 2; Journal ID: ISSN 0002-7863
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; 74 ATOMIC AND MOLECULAR PHYSICS; ACETYLCHOLINE; CATIONS; CHLORIDES; CONSTRUCTION; CRYSTAL STRUCTURE; ELECTROSTATICS; FREE ENERGY; HYDRATION; PROTEINS; RECEPTORS; RESIDUES; RESOLUTION; SODIUM; SODIUM IONS; TRANSPORT; ion channel; ion selectivity; potential of mean force; molecular dynamics

Citation Formats

Fritsch, Sebastian M, Ivanov, Ivaylo N, Wang, Hailong, and Cheng, Xiaolin. Ion Selectivity Mechanism in a Bacterial Pentameric Ligand-Gated Ion Channel. United States: N. p., 2011. Web. doi:10.1016/j.bpj.2010.11.077.
Fritsch, Sebastian M, Ivanov, Ivaylo N, Wang, Hailong, & Cheng, Xiaolin. Ion Selectivity Mechanism in a Bacterial Pentameric Ligand-Gated Ion Channel. United States. doi:10.1016/j.bpj.2010.11.077.
Fritsch, Sebastian M, Ivanov, Ivaylo N, Wang, Hailong, and Cheng, Xiaolin. Sat . "Ion Selectivity Mechanism in a Bacterial Pentameric Ligand-Gated Ion Channel". United States. doi:10.1016/j.bpj.2010.11.077.
@article{osti_1042763,
title = {Ion Selectivity Mechanism in a Bacterial Pentameric Ligand-Gated Ion Channel},
author = {Fritsch, Sebastian M and Ivanov, Ivaylo N and Wang, Hailong and Cheng, Xiaolin},
abstractNote = {The proton-gated ion channel from Gloeobacter violaceus (GLIC) is a prokaryotic homolog of the eukaryotic nicotinic acetylcholine receptor (nAChR) that responds to the binding of neurotransmitter acetylcholine and mediates fast signal transmission. Recent emergence of a high resolution crystal structure of GLIC captured in a potentially open state allowed detailed, atomic-level insight into ion conduction and selectivity mechanisms in these channels. Herein, we have examined the barriers to ion conduction and origins of ion selectivity in the GLIC channel by the construction of potential of mean force (PMF) profiles for sodium and chloride ions inside the transmembrane region. Our calculations reveal that the GLIC channel is open for a sodium ion to transport, but presents a ~10 kcal/mol free energy barrier for a chloride ion, which arises primarily from the unfavorable interactions with a ring of negatively charged glutamate residues (E-2 ) at the intracellular end and a ring of hydrophobic residues (I9 ) in the middle of the transmembrane domain. Our collective findings further suggest that the charge selection mechanism can, to a large extent, be attributed to the narrow intracellular end and a ring of glutamate residues in this position their strong negative electrostatics and ability to bind cations. By contrast, E19 at the extracellular entrance only plays a minor role in ion selectivity of GLIC. In addition to electrostatics, both ion hydration and protein dynamics are found to be crucial for ion conduction as well, which explains why a chloride ion experiences a much greater barrier than a sodium ion in the hydrophobic region of the pore.},
doi = {10.1016/j.bpj.2010.11.077},
journal = {Journal of the American Chemical Society},
issn = {0002-7863},
number = 2,
volume = 100,
place = {United States},
year = {2011},
month = {1}
}