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

Journal Article · Sat Jan 01 00:00:00 EST 2011 · Journal of the American Chemical Society

DOI:https://doi.org/10.1016/j.bpj.2010.11.077· OSTI ID:1042763

Fritsch, Sebastian M ^[1]; Ivanov, Ivaylo N ^[1]; Wang, Hailong ^[2]; Cheng, Xiaolin ^[1]

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1. ORNL
2. Mayo Clinic College of Medicine

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.

• Research Organization: Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Oak Ridge Leadership Computing Facility (OLCF); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). National Center for Computational Sciences (NCCS)
• Sponsoring Organization: USDOE Office of Science (SC)
• DOE Contract Number: DE-AC05-00OR22725
• OSTI ID: 1042763
• Journal Information: Journal of the American Chemical Society, Vol. 100, Issue 2; ISSN 0002-7863
• Country of Publication: United States
• Language: English

Related Subjects

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