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A two-domain elevator mechanism for sodium/proton antiport

Nature volume 501, pages 573–577 (2013)Cite this article

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Abstract

Sodium/proton (Na+/H+) antiporters, located at the plasma membrane in every cell, are vital for cell homeostasis1. In humans, their dysfunction has been linked to diseases, such as hypertension, heart failure and epilepsy, and they are well-established drug targets2. The best understood model system for Na+/H+ antiport is NhaA from Escherichia coli1,3, for which both electron microscopy and crystal structures are available4,5,6. NhaA is made up of two distinct domains: a core domain and a dimerization domain. In the NhaA crystal structure a cavity is located between the two domains, providing access to the ion-binding site from the inward-facing surface of the protein1,4. Like many Na+/H+ antiporters, the activity of NhaA is regulated by pH, only becoming active above pH 6.5, at which point a conformational change is thought to occur7. The only reported NhaA crystal structure so far is of the low pH inactivated form4. Here we describe the active-state structure of a Na+/H+ antiporter, NapA from Thermus thermophilus, at 3 Å resolution, solved from crystals grown at pH 7.8. In the NapA structure, the core and dimerization domains are in different positions to those seen in NhaA, and a negatively charged cavity has now opened to the outside. The extracellular cavity allows access to a strictly conserved aspartate residue thought to coordinate ion binding1,8,9 directly, a role supported here by molecular dynamics simulations. To alternate access to this ion-binding site, however, requires a surprisingly large rotation of the core domain, some 20° against the dimerization interface. We conclude that despite their fast transport rates of up to 1,500 ions per second3, Na+/H+ antiporters operate by a two-domain rocking bundle model, revealing themes relevant to secondary-active transporters in general.

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Figure 1: NapA Na+/H+ transport activity is electrogenic.
Figure 2: Outward-facing NapA structure.
Figure 3: Structure of NapA dimer and proposed Na+/(Li+)-binding site.
Figure 4: Alternating access model of sodium-proton antiport.

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Protein Data Bank

Data deposits

The coordinates and the structure factors for NapA have been deposited in the Protein Data Bank under accession code 4BWZ.

References

  1. Padan, E. The enlightening encounter between structure and function in the NhaA Na+-H+ antiporter. Trends Biochem. Sci. 33, 435–443 (2008)

    Article  CAS  PubMed  Google Scholar 

  2. Brett, C. L., Donowitz, M. & Rao, R. Evolutionary origins of eukaryotic sodium/proton exchangers. Am. J. Physiol. Cell Physiol. 288, C223–C239 (2005)

    Article  CAS  PubMed  Google Scholar 

  3. Taglicht, D., Padan, E. & Schuldiner, S. Overproduction and purification of a functional Na+/H+ antiporter coded by nhaA (ant) from Escherichia coli. J. Biol. Chem. 266, 11289–11294 (1991)

    CAS  PubMed  Google Scholar 

  4. Hunte, C. et al. Structure of a Na+/H+ antiporter and insights into mechanism of action and regulation by pH. Nature 435, 1197–1202 (2005)

    Article  CAS  ADS  PubMed  Google Scholar 

  5. Williams, K. A., Geldmacher-Kaufer, U., Padan, E., Schuldiner, S. & Kuhlbrandt, W. Projection structure of NhaA, a secondary transporter from Escherichia coli, at 4.0 Å resolution. EMBO J. 18, 3558–3563 (1999)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Williams, K. A. Three-dimensional structure of the ion-coupled transport protein NhaA. Nature 403, 112–115 (2000)

    Article  CAS  ADS  PubMed  Google Scholar 

  7. Kozachkov, L. & Padan, E. Conformational changes in NhaA Na+/H+ antiporter. Mol. Membr. Biol. 30, 90–100 (2012)

    Article  PubMed  Google Scholar 

  8. Arkin, I. T. et al. Mechanism of Na+/H+ antiporting. Science 317, 799–803 (2007)

    Article  CAS  ADS  PubMed  Google Scholar 

  9. Maes, M., Rimon, A., Kozachkov-Magrisso, L., Friedler, A. & Padan, E. Revealing the ligand binding site of NhAa Na+/H+ antiporter and its pH dependence. J. Biol. Chem. 287, 38150–38157 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. West, I. C. & Mitchell, P. Proton/sodium ion antiport in Escherichia coli. Biochem. J. 144, 87–90 (1974)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Taglicht, D., Padan, E. & Schuldiner, S. Proton-sodium stoichiometry of NhaA, an electrogenic antiporter from Escherichia coli. J. Biol. Chem. 268, 5382–5387 (1993)

    CAS  PubMed  Google Scholar 

  12. Pinner, E., Padan, E. & Schuldiner, S. Kinetic properties of NhaB, a Na+/H+ antiporter from Escherichia coli. J. Biol. Chem. 269, 26274–26279 (1994)

    CAS  PubMed  Google Scholar 

  13. Drew, D., Lerch, M., Kunji, E., Slotboom, D. J. & de Gier, J. W. Optimization of membrane protein overexpression and purification using GFP fusions. Nature Methods 3, 303–313 (2006)

    Article  CAS  PubMed  Google Scholar 

  14. Sonoda, Y. et al. Benchmarking membrane protein detergent stability for improving throughput of high-resolution X-ray structures. Structure 19, 17–25 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Furrer, E. M., Ronchetti, M. F., Verrey, F. & Pos, K. M. Functional characterization of a NapA Na+/H+ antiporter from Thermus thermophilus. FEBS Lett. 581, 572–578 (2007)

    Article  CAS  PubMed  Google Scholar 

  16. Padan, E. et al. NhaA of Escherichia coli, as a model of a pH-regulated Na+/H+ antiporter. Biochim. Biophys. Acta 1658, 2–13 (2004)

    Article  CAS  PubMed  Google Scholar 

  17. Rimon, A., Tzubery, T. & Padan, E. Monomers of the NhaA Na+/H+ antiporter of Escherichia coli are fully functional yet dimers are beneficial under extreme stress conditions at alkaline pH in the presence of Na+ or Li+. J. Biol. Chem. 282, 26810–26821 (2007)

    Article  CAS  PubMed  Google Scholar 

  18. Hisamitsu, T., Ben Ammar, Y., Nakamura, T. Y. & Wakabayashi, S. Dimerization is crucial for the function of the Na+/H+ exchanger NHE1. Biochemistry 45, 13346–13355 (2006)

    Article  CAS  PubMed  Google Scholar 

  19. Appel, M., Hizlan, D., Vinothkumar, K. R., Ziegler, C. & Kuhlbrandt, W. Conformations of NhaA, the Na+/H+ exchanger from Escherichia coli, in the pH-activated and ion-translocating states. J. Mol. Biol. 388, 659–672 (2009)

    Article  CAS  PubMed  Google Scholar 

  20. Goswami, P. et al. Structure of the archaeal Na+/H+ antiporter NhaP1 and functional role of transmembrane helix 1. EMBO J. 30, 439–449 (2011)

    Article  CAS  PubMed  Google Scholar 

  21. Kuwabara, N., Inoue, H., Tsuboi, Y., Nakamura, N. & Kanazawa, H. The fourth transmembrane domain of the Helicobacter pylori Na+/H+ antiporter NhaA faces a water-filled channel required for ion transport. J. Biol. Chem. 279, 40567–40575 (2004)

    Article  CAS  PubMed  Google Scholar 

  22. Mager, T., Rimon, A., Padan, E. & Fendler, K. Transport Mechanism and pH Regulation of the Na+/H+ Antiporter NhaA from Escherichia coli. J. Biol. Chem. 286, 23570–23581 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Screpanti, E. & Hunte, C. Discontinuous membrane helices in transport proteins and their correlation with function. J. Struct. Biol. 159, 261–267 (2007)

    Article  CAS  PubMed  Google Scholar 

  24. Hu, N. J., Iwata, S., Cameron, A. D. & Drew, D. Crystal structure of a bacterial homologue of the bile acid sodium symporter ASBT. Nature 478, 408–411 (2011)

    Article  CAS  ADS  PubMed  PubMed Central  Google Scholar 

  25. Noumi, T., Inoue, H., Sakurai, T., Tsuchiya, T. & Kanazawa, H. Identification and characterization of functional residues in a Na+/H+ antiporter (NhaA) from Escherichia coli by random mutagenesis. J. Biochem. 121, 661–670 (1997)

    Article  CAS  PubMed  Google Scholar 

  26. Vinothkumar, K. R., Smits, S. H. & Kuhlbrandt, W. pH-induced structural change in a sodium/proton antiporter from Methanococcus jannaschii. EMBO J. 24, 2720–2729 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Reyes, N., Ginter, C. & Boudker, O. Transport mechanism of a bacterial homologue of glutamate transporters. Nature 462, 880–885 (2009)

    Article  CAS  ADS  PubMed  PubMed Central  Google Scholar 

  28. Schushan, M. et al. A model-structure of a periplasm-facing state of the NhaA antiporter suggests the molecular underpinnings of pH-induced conformational changes. J. Biol. Chem. 287, 18249–18261 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Drew, D. E., von Heijne, G., Nordlund, P. & de Gier, J. W. Green fluorescent protein as an indicator to monitor membrane protein overexpression in Escherichia coli. FEBS Lett. 507, 220–224 (2001)

    Article  CAS  PubMed  Google Scholar 

  30. Kawate, T. & Gouaux, E. Fluorescence-detection size-exclusion chromatography for precrystallization screening of integral membrane proteins. Structure 14, 673–681 (2006)

    Article  CAS  PubMed  Google Scholar 

  31. Wagner, S. et al. Tuning Escherichia coli for membrane protein overexpression. Proc. Natl Acad. Sci. USA 105, 14371–14376 (2008)

    Article  CAS  ADS  PubMed  PubMed Central  Google Scholar 

  32. Studier, F. W. Protein production by auto-induction in high density shaking cultures. Protein Expr. Purif. 41, 207–234 (2005)

    Article  CAS  PubMed  Google Scholar 

  33. Drew, D. et al. GFP-based optimization scheme for the overexpression and purification of eukaryotic membrane proteins in Saccharomyces cerevisiae. Nature Protocols 3, 784–798 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Slotboom, D. J., Duurkens, R. H., Olieman, K. & Erkens, G. B. Static light scattering to characterize membrane proteins in detergent solution. Methods 46, 73–82 (2008)

    Article  CAS  PubMed  Google Scholar 

  35. Wiedenmann, A., Dimroth, P. & von Ballmoos, C. Functional asymmetry of the F0 motor in bacterial ATP synthases. Mol. Microbiol. 72, 479–490 (2009)

    Article  CAS  PubMed  Google Scholar 

  36. Ishmukhametov, R. R., Galkin, M. A. & Vik, S. B. Ultrafast purification and reconstitution of His-tagged cysteine-less Escherichia coli F1Fo ATP synthase. Biochim. Biophys. Acta 1706, 110–116 (2005)

    Article  CAS  PubMed  Google Scholar 

  37. Wiedenmann, A., Dimroth, P. & von Ballmoos, C. Δψ and ΔpH are equivalent driving forces for proton transport through isolated F0 complexes of ATP synthases. Biochim. Biophys. Acta 1777, 1301–1310 (2008)

    Article  CAS  PubMed  Google Scholar 

  38. Winter, G. xia2: an expert system for macromolecular crystallography data reduction. J. Appl. Crystallogr. 43, 186–190 (2010)

    Article  CAS  Google Scholar 

  39. Kabsch, W. XDS. Acta Crystallogr. D 66, 125–132 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Collaborative Computational Project Number 4. The CCP4 suite: programs for protein crystallography. Acta Crystallogr. D 50, 760–763 (1994)

  41. Knight, S. D. RSPS version 4.0: a semi-interactive vector-search program for solving heavy-atom derivatives. Acta Crystallogr. D 56, 42–47 (2000)

    Article  CAS  PubMed  Google Scholar 

  42. Bricogne, G., Vonrhein, C., Flensburg, C., Schiltz, M. & Paciorek, W. Generation, representation and flow of phase information in structure determination: recent developments in and around SHARP 2.0. Acta Crystallogr. D 59, 2023–2030 (2003)

    Article  CAS  PubMed  Google Scholar 

  43. Cowtan, K. ‘dm’: An automated procedure for phase improvement by density modification. Joint CCP4 ESF-EACBM Newslett. Prot. Crystallogr. 31, 34–38 (1994)

    Google Scholar 

  44. Jones, T. A., Kjeldgaard, M., Charles, W. C., Jr & Robert, M. S. Electron-density map interpretation. Methods Enzymol. 277, 173–208 (1997)

    Article  CAS  PubMed  Google Scholar 

  45. McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658–674 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D 60, 2126–2132 (2004)

    PubMed  Google Scholar 

  47. Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D 66, 213–221 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kleywegt, G. J. & Jones, T. A. A super position. Joint CCP4 ESF-EACBM Newslett. Prot. Crystallogr. 31, 9–14 (1994)

    Google Scholar 

  49. Delano, W. L. The PyMOL Molecular Graphics System (DeLano Scientific, 2002)

  50. Potterton, L. et al. Developments in the CCP4 molecular-graphics project. Acta Crystallogr. D 60, 2288–2294 (2004)

    Article  CAS  PubMed  Google Scholar 

  51. Hess, B., Kutzner, C., van der Spoel, D. & Lindahl, E. GROMACS 4: Algorithms for highly efficient, load-balanced, and scalable molecular simulation. J. Chem. Theory Comput. 4, 435–447 (2008)

    Article  CAS  PubMed  Google Scholar 

  52. MacKerell, A. et al. All-atom empirical potential for molecular modeling and dynamics studies of proteins. J. Phys. Chem. B 102, 3586–3616 (1998)

    Article  CAS  PubMed  Google Scholar 

  53. Mackerell, J. A. D., Jr, Feig, M. & Brooks, C. L., III Extending the treatment of backbone energetics in protein force fields: limitations of gas-phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations. J. Comput. Chem. 25, 1400–1415 (2004)

    Article  CAS  PubMed  Google Scholar 

  54. Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W. & Klein, M. L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 79, 926–935 (1983)

    Article  CAS  ADS  Google Scholar 

  55. Klauda, J. B. et al. Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types. J. Phys. Chem. B 114, 7830–7843 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Stansfeld, P. J. & Sansom, M. S. P. From coarse grained to atomistic: a serial multiscale approach to membrane protein simulations. J. Chem. Theory Comput. 7, 1157–1166 (2011)

    Article  CAS  PubMed  Google Scholar 

  57. Bond, P. J., Wee, C. L. & Sansom, M. S. P. Coarse-grained molecular dynamics simulations of the energetics of helix insertion into a lipid bilayer. Biochemistry 47, 11321–11331 (2008)

    Article  CAS  PubMed  Google Scholar 

  58. Scott, K. A. et al. Coarse-grained MD simulations of membrane protein-bilayer self-assembly. Structure 16, 621–630 (2008)

    Article  CAS  PubMed  Google Scholar 

  59. Li, H., Robertson, A. D. & Jensen, J. H. Very fast empirical prediction and rationalization of protein pKa values. Proteins 61, 704–721 (2005)

    Article  CAS  PubMed  Google Scholar 

  60. Bussi, G., Donadio, D. & Parrinello, M. Canonical sampling through velocity rescaling. J. Chem. Phys. 126, 014101 (2007)

    Article  ADS  CAS  PubMed  Google Scholar 

  61. Parrinello, M. & Rahman, A. Polymorphic transitions in single crystals: A new molecular dynamics method. J. Appl. Phys. 52, 7182–7190 (1981)

    Article  CAS  ADS  Google Scholar 

  62. Hess, B. P-LINCS: a parallel linear constraint solver for molecular simulation. J. Chem. Theory Comput. 4, 116–122 (2008)

    Article  CAS  PubMed  Google Scholar 

  63. Essmann, U. et al. A smooth particle mesh Ewald method. J. Chem. Phys. 103, 8577–8592 (1995)

    Article  CAS  ADS  Google Scholar 

  64. Miyamoto, S. & Kollman, P. A. SETTLE: An analytical version of the SHAKE and RATTLE algorithms for rigid water models. J. Comput. Chem. 13, 952–962 (1992)

    Article  CAS  Google Scholar 

  65. Michaud-Agrawal, N., Denning, E. J., Woolf, T. B. & Beckstein, O. MDAnalysis: a toolkit for the analysis of molecular dynamics simulations. J. Comput. Chem. 32, 2319–2327 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Humphrey, W., Dalke, A. & Schulten, K. VMD—visual molecular dynamics. J. Mol. Graph. 14, 33–38 (1996)

    Article  CAS  PubMed  Google Scholar 

  67. Dahl, A. C. E., Chavent, M. & Sansom, M. S. P. Bendix: Intuitive helix geometry analysis and abstraction for VMD. Bioinformatics 28, 2193–2194 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Pettersen, E. F. et al. UCSF Chimera–a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004)

    Article  CAS  PubMed  Google Scholar 

  69. Goddard, T. D., Huang, C. C. & Ferrin, T. E. Visualizing density maps with UCSF Chimera. J. Struct. Biol. 157, 281–287 (2007)

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We are grateful to D. Slotboom for critical reading of the manuscript and N.-J. Hu for assistance in data collection. Data were collected at the European Synchrotron Radiation Facility and Diamond Light Source, with excellent assistance from beamline scientists. This work was funded by grants from the Medical Research Council (MRC grant G0900990 to A.D.C. and D.D.), the Swedish Research Council (to C.v.B. and D.D.) and the BBSRC (BB/G02325/1 to S.I.). The authors are grateful for the use of the Membrane Protein Laboratory funded by the Wellcome Trust (grant 062164/Z/00/Z) at the Diamond Light Source Limited and The Centre for Biomembrane Research (CBR), supported by the Swedish Foundation for Strategic Research. Computer simulations were partially run on XSEDE resources (grant TG-MCB120151 to O.B.). C.L. was a recipient of a BBSRC-funded PhD scholarship, H.J.K. a Human Frontiers Science Program (HFSP) postdoctoral fellowship, and D.D. acknowledges the support from The Royal Society through the University Research Fellow (URF) scheme.

Author information

Author notes

  1. Simon Newstead

    Present address: Present address: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.,

  2. d.drew@imperial.ac.uk

  3. ddrew@dbb.su.se

Authors and Affiliations

  1. Division of Molecular Biosciences, Imperial College London, London SW7 2AZ, UK,

    Chiara Lee, Hae Joo Kang, Simon Newstead, So Iwata, Alexander D. Cameron & David Drew

  2. Department of Biochemistry and Biophysics, Centre for Biomembrane Research, Stockholm University, SE-106 91 Stockholm, Sweden,

    Christoph von Ballmoos, Povilas Uzdavinys & David Drew

  3. Department of Physics, Center for Biological Physics, Arizona State University, Tempe, 85287-1504, Arizona, USA

    David L. Dotson & Oliver Beckstein

  4. Membrane Protein Laboratory, Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Chilton, Oxfordshire OX11 0DE, UK,

    So Iwata & Alexander D. Cameron

  5. Research Complex at Harwell Rutherford, Appleton Laboratory, Harwell, Oxford, Didcot, Oxfordshire OX11 0FA, UK,

    So Iwata & Alexander D. Cameron

  6. School of Life Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK,

    Alexander D. Cameron

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Contributions

A.D.C. and D.D. designed the project. Cloning, expression screening, protein purification and crystallization were carried out by C.L. and D.D. with assistance from H.J.K., S.N., S.I. and A.D.C. Data collection and structural determination were carried out by C.L., D.D. and A.D.C. Experiments for functional analysis were designed by C.v.B. and D.D. and carried out by C.v.B., C.L., P.U. and D.D. Molecular dynamics simulations were carried out by D.L.D. and O.B. A.D.C. and D.D. wrote the manuscript with contributions from C.L., H.J.K., C.v.B. and O.B.

Corresponding authors

Correspondence to Alexander D. Cameron or David Drew.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-8, Supplementary Tables 1-2 and additional references. (PDF 9005 kb)

Alternating access model of Na+/H+ antiport.

Video morphing between the outward-facing NapA crystal structure and a model created by superposing the NapA Core and Dimerisation domains separately onto the NhaA structure. The residues mentioned in the text are shown in a stick representation. Colouring as in Figure 3. (MOV 5509 kb)

Alternating access model of Na+/H+ antiport.

Video morphing between the outward-facing NapA crystal structure and a model created by superposing the NapA Core and Dimerisation domains separately onto the NhaA structure. The residues mentioned in the text are shown in a stick representation. Colouring as in Figure 3. (MOV 8207 kb)

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Lee, C., Kang, H., von Ballmoos, C. et al. A two-domain elevator mechanism for sodium/proton antiport. Nature 501, 573–577 (2013). https://doi.org/10.1038/nature12484

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