title: Electrostatics of ion stabilization in a ClC chloride channel homologue from Escherichia coli.
abstract: The structural determinants of electrostatics of ion stabilization within EcClC, a ClC-type chloride channel homologue from Escherichia coli, are studied using a continuum dielectric approximation. Specifically, the ion occupancy is investigated in the wild-type protein and a mutant thereof, and the contribution to the electrostatic binding free energy of local and non-local interactions is characterized at the single-residue level. This analysis shows that, in spite of the desolvation cost and the strong ion-ion repulsion, all previously reported binding sites can be occupied simultaneously. The stabilizing effect of the protein arises from hydrogen bonding as well as from longer-range favorable interactions, such as with the strictly conserved Lys131 side-chain. The latter is involved in the stabilization of the conserved GSGIP motif that delimits two of the binding sites. Interestingly, an additional low-affinity binding site, mediated by a structurally analogous motif including the side-chain of Arg340, can be identified on the extracellular side of the permeation pathway. Finally, it is shown that, in contrast to K-channels, and in analogy to the SBP/PBP sulfate/phosphate-binding proteins, the contribution of helix macrodipoles to chloride binding in EcClC is only marginal.
authors.affiliation: Department of Biochemistry, Weill Medical College of Cornell University, Whitney Building, 1300 York Avenue, New York, NY 10021, USA.
authors.forename: José D
authors.initials: JD
authors.lastname: Faraldo-Gómez
authors.forename: Benoît
authors.initials: B
authors.lastname: Roux
mesh_terms: D000595:Amino Acid Sequence; D018118:Chloride Channels / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
chemical_list: D018118:Chloride Channels