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  • 标题:Molecular mechanism of proton transport in CLC Cl-/H+ exchange transporters
  • 本地全文:下载
  • 作者:Liang Feng ; Ernest B. Campbell ; Roderick MacKinnon
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2012
  • 卷号:109
  • 期号:29
  • 页码:11699-11704
  • DOI:10.1073/pnas.1205764109
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要: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.
  • 关键词:chloride ; proton exchange ; antiporter
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