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

Feng, Liang, Campbell, Ernest B., MacKinnon, Roderick·2012·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1205764109
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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.

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Research works printed but not linked: 33

  1. M Maduke, C Miller, JA Mindell, A decade of CLC chloride channels: Structure, mechanism, and many unsettled questions. Annu Rev Biophys Biomol Struct 29, 411–438 (2000). · DOI
  2. TJ Jentsch, CLC chloride channels and transporters: From genes to protein structure, pathology and physiology. Crit Rev Biochem Mol Biol 43, 3–36 (2008). · DOI
  3. G Zifarelli, M Pusch, CLC chloride channels and transporters: A biophysical and physiological perspective. Rev Physiol Biochem Pharmacol 158, 23–76 (2007). · DOI
  4. TY Chen, TC Hwang, CLC-0 and CFTR: Chloride channels evolved from transporters. Physiol Rev 88, 351–387 (2008). · DOI
  5. A Accardi, C Miller, Secondary active transport mediated by a prokaryotic homologue of ClC Cl- channels. Nature 427, 803–807 (2004). · DOI
  6. A Picollo, M Pusch, Chloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5. Nature 436, 420–423 (2005). · DOI
  7. O Scheel, AA Zdebik, S Lourdel, TJ Jentsch, Voltage-dependent electrogenic chloride/proton exchange by endosomal CLC proteins. Nature 436, 424–427 (2005). · DOI
  8. R Dutzler, A structural perspective on ClC channel and transporter function. FEBS Lett 581, 2839–2844 (2007). · DOI
  9. C Miller, W Nguitragool, A provisional transport mechanism for a chloride channel-type Cl-/H+ exchanger. Philos Trans R Soc Lond B Biol Sci 364, 175–180 (2009). · DOI
  10. DC Gadsby, Ion channels versus ion pumps: The principal difference, in principle. Nat Rev Mol Cell Biol 10, 344–352 (2009). · DOI
  11. MF Chen, TY Chen, Side-chain charge effects and conductance determinants in the pore of ClC-0 chloride channels. J Gen Physiol 122, 133–145 (2003). · DOI
  12. R Estevez, BC Schroeder, A Accardi, TJ Jentsch, M Pusch, Conservation of chloride channel structure revealed by an inhibitor binding site in ClC-1. Neuron 38, 47–59 (2003). · DOI
  13. AM Engh, M Maduke, Cysteine accessibility in ClC-0 supports conservation of the ClC intracellular vestibule. J Gen Physiol 125, 601–617 (2005). · DOI
  14. R Dutzler, EB Campbell, M Cadene, BT Chait, R MacKinnon, X-ray structure of a ClC chloride channel at 3.0 Å reveals the molecular basis of anion selectivity. Nature 415, 287–294 (2002). · DOI · Paper page
  15. R Dutzler, EB Campbell, R MacKinnon, Gating the selectivity filter in ClC chloride channels. Science 300, 108–112 (2003). · DOI · Paper page
  16. L Feng, EB Campbell, Y Hsiung, R MacKinnon, Structure of a eukaryotic CLC transporter defines an intermediate state in the transport cycle. Science 330, 635–641 (2010). · DOI · Paper page
  17. A Accardi, L Kolmakova-Partensky, C Williams, C Miller, Ionic currents mediated by a prokaryotic homologue of CLC Cl- channels. J Gen Physiol 123, 109–119 (2004). · DOI
  18. C Miller, ClC chloride channels viewed through a transporter lens. Nature 440, 484–489 (2006). · DOI
  19. G Zifarelli, AR Murgia, P Soliani, M Pusch, Intracellular proton regulation of ClC-0. J Gen Physiol 132, 185–198 (2008). · DOI
  20. J Zhang, Y Feng, M Forgac, Proton conduction and bafilomycin binding by the V0 domain of the coated vesicle V-ATPase. J Biol Chem 269, 23518–23523 (1994). · DOI
  21. JJ Matsuda, et al., Overexpression of CLC-3 in HEK293T cells yields novel currents that are pH dependent. Am J Physiol Cell Physiol 294, C251–C262 (2008). · DOI
  22. I Neagoe, T Stauber, P Fidzinski, E-Y Bergsdorf, TJ Jentsch, The late endosomal CLC-6 mediates proton/chloride countertransport in heterologous plasma membrane expression. J Biol Chem 285, 21689–21697 (2010). · DOI
  23. A Accardi, et al., Separate ion pathways in a Cl-/H+ exchanger. J Gen Physiol 126, 563–570 (2005). · DOI
  24. HH Lim, C Miller, Intracellular proton-transfer mutants in a CLC Cl-/H+ exchanger. J Gen Physiol 133, 131–138 (2009). · DOI
  25. A Picollo, M Malvezzi, JC Houtman, A Accardi, Basis of substrate binding and conservation of selectivity in the CLC family of channels and transporters. Nat Struct Mol Biol 16, 1294–1301 (2009). · DOI
  26. R MacKinnon, Potassium channels. FEBS lett 555, 62–65 (2003). · DOI
  27. S Lobet, R Dutzler, Ion-binding properties of the ClC chloride selectivity filter. EMBO J 25, 24–33 (2006). · DOI
  28. H Jayaram, A Accardi, F Wu, C Williams, C Miller, Ion permeation through a Cl-selective channel designed from a CLC Cl-/H+ exchanger. Proc Natl Acad Sci USA 105, 11194–11199 (2008). · DOI · Paper page
  29. Z Otwinowski, W Minor, Processing of X-ray diffraction data collected in oscillation mode. Methods in Enzymology, eds CW Carter, RM Sweet (Academic Press, New York) Vol 276, 307–326 (1997).
  30. AJ Mccoy, et al., Phaser crystallographic software. J Appl Crystallogr 40, 658–674 (2007). · DOI · Paper page
  31. PD Adams, et al., PHENIX: A comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66, 213–221 (2010). · DOI · Paper page
  32. V Ruta, Y Jiang, A Lee, J Chen, R MacKinnon, Functional analysis of an archaebacterial voltage-dependent K+ channel. Nature 422, 180–185 (2003). · DOI
  33. CM Nimigean, A radioactive uptake assay to measure ion transport across ion channel-containing liposomes. Nat Protoc 1, 1207–1212 (2006). · DOI

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Metadata

Authors
Feng, L., Campbell, E. B., & MacKinnon, R.
Affiliations
Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2012-07-02
Volume
109
Issue
29
Pages
11699-11704
ISSN
  • 0027-8424
  • 1091-6490
DOI
10.1073/pnas.1205764109
Cited by
82
References
1
Language
en

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