Key result
Mutation of residue R147 to C147 in the EcClC chloride channel made the electrostatic potential around the selectivity filter more negative and decreased chloride ion stabilization at binding sites.
Mutation of the R147 residue in the EcClC chloride channel decreases chloride ion stabilization at binding sites, potentially affecting channel gating.
The effect of mutation of strongly conserved porelining residues in the chloride channel EcClC on the electrostatic potential and binding free energy of the chloride ion was studied using explicit protein-membrane structures. Electrostatic potential distribution and binding free energy of the chloride ion at different binding sites in the wild-type and mutated EcClC were calculated with APBS. The potential data reveal that the electrostatic potential around the selectivity filter, especially around the site S ext and S cen becomes more negative as the residue R147 was mutated to C147. The electrostatic binding free energy shows that the binding free energy of the chloride ion at all binding sites becomes more positive as R147 was mutated. It follows that mutation of R147 decreases ion stabilization at binding sites and affects channel’s gating.
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Zou et al. (2007) studied this question. Mutation of residue R147 to C147 vs. Wild-type EcClC was evaluated on Electrostatic potential and binding free energy of the chloride ion. Mutation of residue R147 to C147 in the EcClC chloride channel made the electrostatic potential around the selectivity filter more negative and decreased chloride ion stabilization at binding sites.
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