Conduction mechanisms of chloride ions in ClC-type channels

被引:63
作者
Corry, B [1 ]
O'Mara, M [1 ]
Chung, SH [1 ]
机构
[1] Australian Natl Univ, Res Sch Phys Sci, Dept Theoret Phys, Canberra, ACT 0200, Australia
基金
澳大利亚研究理事会; 英国医学研究理事会;
关键词
D O I
10.1016/S0006-3495(04)74160-0
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
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 Angstrom. 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.
引用
收藏
页码:846 / 860
页数:15
相关论文
共 51 条
[11]   IONIC SELECTIVITY, SATURATION, AND BLOCK IN A K+-SELECTIVE CHANNEL FROM SARCOPLASMIC-RETICULUM [J].
CORONADO, R ;
ROSENBERG, RL ;
MILLER, C .
JOURNAL OF GENERAL PHYSIOLOGY, 1980, 76 (04) :425-446
[12]   Dielectric self-energy in Poisson-Boltzmann and Poisson-Nernst-Planck models of ion channels [J].
Corry, B ;
Kuyucak, S ;
Chung, SH .
BIOPHYSICAL JOURNAL, 2003, 84 (06) :3594-3606
[13]   Mechanisms of permeation and selectivity in calcium channels [J].
Corry, B ;
Allen, TW ;
Kuyucak, S ;
Chung, SH .
BIOPHYSICAL JOURNAL, 2001, 80 (01) :195-214
[14]   The structure of the potassium channel:: Molecular basis of K+ conduction and selectivity [J].
Doyle, DA ;
Cabral, JM ;
Pfuetzner, RA ;
Kuo, AL ;
Gulbis, JM ;
Cohen, SL ;
Chait, BT ;
MacKinnon, R .
SCIENCE, 1998, 280 (5360) :69-77
[15]   A serine residue in CIG-3 links phosphorylation-dephosphorylation to chloride channel regulation by cell volume [J].
Duan, D ;
Cowley, S ;
Horowitz, B ;
Hume, JR .
JOURNAL OF GENERAL PHYSIOLOGY, 1999, 113 (01) :57-70
[16]   X-ray structure of a CIC chloride channel at 3.0 Å reveals the molecular basis of anion selectivity [J].
Dutzler, R ;
Campbell, EB ;
Cadene, M ;
Chait, BT ;
MacKinnon, R .
NATURE, 2002, 415 (6869) :287-294
[17]   Gating the selectivity filter in ClC chloride channels [J].
Dutzler, R ;
Campbell, EB ;
MacKinnon, R .
SCIENCE, 2003, 300 (5616) :108-112
[18]   Continuum electrostatics fails to describe ion permeation in the gramicidin channel [J].
Edwards, S ;
Corry, B ;
Kuyucak, S ;
Chung, SH .
BIOPHYSICAL JOURNAL, 2002, 83 (03) :1348-1360
[19]   Conservation of chloride channel structure revealed by an inhibitor binding site in CIC-1 [J].
Estévez, R ;
Schroeder, BC ;
Accardi, A ;
Jentsch, TJ ;
Pusch, M .
NEURON, 2003, 38 (01) :47-59
[20]   AN ASPARTIC-ACID RESIDUE IMPORTANT FOR VOLTAGE-DEPENDENT GATING OF HUMAN MUSCLE CHLORIDE CHANNELS [J].
FAHLKE, C ;
RUDEL, R ;
MITROVIC, N ;
ZHOU, M ;
GEORGE, AL .
NEURON, 1995, 15 (02) :463-472