title: Molecular mechanism of proton transport in CLC Cl-/H+ exchange transporters.
abstract: CLC proteins underlie muscle, kidney, bone, and other organ system function by catalyzing the transport of Cl(-) ions across cell and organellar membranes. Some CLC proteins are ion channels while others are pumps that exchange Cl(-) for H(+). The pathway through which Cl(-) ions cross the membrane has been characterized, but the transport of H(+) and the principle by which their movement is coupled to Cl(-) movement is not well understood. Here we show that H(+) transport depends not only on the presence of a specific glutamate residue but also the presence of Cl(-) ions. H(+) transport, however, can be isolated and analyzed in the absence of Cl(-) by mutating the glutamate to alanine and adding carboxylate-containing molecules to solution, consistent with the notion that H(+) transfer is mediated through the entry of a carboxylate group into the anion pathway. Cl(-) ions and carboxylate interact with each other strongly. These data support a mechanism in which the glutamate carboxylate functions as a surrogate Cl(-) ion, but it can accept a H(+) and transfer it between the external solution and the central Cl(-) binding site, coupled to the movement of 2 Cl(-) ions.
authors: Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA.
authors: Liang
authors: L
authors: Feng
authors: Ernest B
authors: EB
authors: Campbell
authors: Roderick
authors: R
authors: MacKinnon
mesh_terms: D000818:Animals; D017920:Antiporters / Q000378:metabolism*; D001693:Biological Transport, Active / Q000502:physiology; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism*; D004926:Escherichia coli; D005453:Fluorescence; D008958:Models, Molecular; D009036:Moths; D011522:Protons
chemical_list: D017920:Antiporters; D002712:Chlorides; D011522:Protons; C114260:hydrogen-chloride symporter