Referenced in: none

Automatically associated channels: ClC4

Title: A provisional transport mechanism for a chloride channel-type Cl-/H+ exchanger.

Authors: Christopher Miller, Wang Nguitragool

Journal, date & volume: Philos. Trans. R. Soc. Lond., B, Biol. Sci., 2009 Jan 27 , 364, 175-80

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18977737

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-.