The fast gating mechanism in ClC-0 channels

Date

2005-07

Authors

Bisset, David
Corry, Ben
Chung, Shin-Ho

Journal Title

Journal ISSN

Volume Title

Publisher

Biophysical Society

Abstract

We investigate and then modify the hypothesis that a glutamate side chain acts as the fast gate in ClC-0 channels. We first create a putative open-state configuration of the prokaryotic ClC Cl- channel using its crystallographic structure as a basis. Then, retaining the same pore shape, the prokaryotic ClC channel is converted to ClC-0 by replacing all the nonconserved polar and charged residues. Using this open-state channel model, we carry out molecular dynamics simulations to study how the glutamate side chain can move between open and closed configurations. When the side chain extends toward the extracellular end of the channel, it presents an electrostatic barrier to Cl- conduction. However, external Cl- ions can push the side chain into a more central position where, pressed against the channel wall, it does not impede the motion of Cl- ions. Additionally, a proton from a low-pH external solution can neutralize the extended glutamate side chain, which also removes the barrier to conduction. Finally, we use Brownian dynamics simulations to demonstrate the influence of membrane potential and external Cl- concentration on channel open probability.

Description

Keywords

biophysics, chlorides, chlorine, computer simulation, crystallography, x-ray, escherichia coli, glutamic acid, gramicidin, hydrogen-ion concentration, ions, membrane potentials, models, molecular, models, theoretical, protein conformation, protein structure, tertiary, protons, time factors, ion channel gating

Citation

Source

Biophysical Journal

Type

Journal article

Book Title

Entity type

Access Statement

Open Access

License Rights

DOI

10.1529/biophysj.104.053447

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