title: A provisional transport mechanism for a chloride channel-type Cl-/H+ exchanger.
abstract: Chloride channel (CLC)-type Cl-/H+ exchangers are widespread throughout the biological world, and one of these, CLC-ec1 from Escherichia coli, has been extensively studied. The structure of this protein is known, and several of its mechanistic hot spots have been identified, but a mechanism for Cl-/H+ exchange has not previously been offered. We herein confirm by direct measurements of Cl- and H+ fluxes a Cl--to-H+ exchange stoichiometry of 2, and summarize experimental facts pertinent to the exchange mechanism. While the mechanism must involve a conformational cycle of alternating exposure of substrate-binding sites to the two sides of the membrane, CLC transporters do not adhere to a familiar ping-pong scheme in which the two ions bind in a mutually exclusive fashion. Instead, Cl- and H+ occupy the ion-binding region simultaneously. A conformational cycle is proposed that accounts for the exchange stoichiometry, several key mutants and the tendency of the protein to become uncoupled and allow 'slippage' of Cl-.
authors.affiliation: Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02454, USA. cmiller@brandeis.edu
authors.forename: Christopher
authors.initials: C
authors.lastname: Miller
authors.forename: Wang
authors.initials: W
authors.lastname: Nguitragool
mesh_terms: D001665:Binding Sites; D018118:Chloride Channels / Q000737:chemistry* / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism*; D006859:Hydrogen / Q000378:metabolism; D015640:Ion Channel Gating; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D021122:Protein Subunits
chemical_list: D018118:Chloride Channels; D002712:Chlorides; C508370:ClC protein, E coli; D029968:Escherichia coli Proteins; D021122:Protein Subunits; D006859:Hydrogen