Details

Autor(en) / Beteiligte

• Feng, Liang
• Campbell, Ernest B
• MacKinnon, Roderick

Titel

Molecular mechanism of proton transport in CLC Cl⁻/H⁺ exchange transporters

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2012-07, Vol.109 (29), p.11699-11704

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2012

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.