title: Conduction mechanisms of chloride ions in ClC-type channels.
abstract: The conduction properties of ClC-0 and ClC-1 chloride channels are examined using electrostatic calculations and three-dimensional Brownian dynamics simulations. We create an open-state configuration of the prokaryotic ClC Cl(-) channel using its known crystallographic structure as a basis. Two residues that are occluding the channel are slowly pushed outward with molecular dynamics to create a continuous ion-conducting path with the minimum radius of 2.5 A. Then, retaining the same pore shape, the prokaryotic ClC channel is converted to either ClC-0 or ClC-1 by replacing all the nonconserved dipole-containing and charged amino acid residues. Employing open-state ClC-0 and ClC-1 channel models, current-voltage curves consistent with experimental measurements are obtained. We find that conduction in these pores involves three ions. We locate the binding sites, as well as pinpointing the rate-limiting steps in conduction, and make testable predictions about how the single channel current across ClC-0 and ClC-1 will vary as the ionic concentrations are increased. Finally, we demonstrate that a ClC-0 homology model created from an alternative sequence alignment fails to replicate any of the experimental observations.
authors.affiliation: Department of Theoretical Physics, Research School of Physical Sciences, The Australian National University, Canberra, Australia.
authors.forename: Ben
authors.initials: B
authors.lastname: Corry
authors.forename: Megan
authors.initials: M
authors.lastname: O'Mara
authors.forename: Shin-Ho
authors.initials: SH
authors.lastname: Chung
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D001665:Binding Sites; D018118:Chloride Channels / Q000737:chemistry*; D002713:Chlorine / Q000737:chemistry*; D003198:Computer Simulation; D004058:Diffusion; D004553:Electric Conductivity; D029968:Escherichia coli Proteins / Q000737:chemistry; D015640:Ion Channel Gating; D007477:Ions / Q000737:chemistry; D008563:Membrane Lipids / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D010539:Permeability; D016062:Porosity; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D055672:Static Electricity; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
chemical_list: D000596:Amino Acids; D018118:Chloride Channels; D029968:Escherichia coli Proteins; D007477:Ions; D008563:Membrane Lipids; D014867:Water; D002713:Chlorine