Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

Overcoming barriers to membrane protein structure determination

Nature Biotechnology volume 29, pages 335–340 (2011)Cite this article

Subjects

Abstract

After decades of slow progress, the pace of research on membrane protein structures is beginning to quicken thanks to various improvements in technology, including protein engineering and microfocus X-ray diffraction. Here we review these developments and, where possible, highlight generic new approaches to solving membrane protein structures based on recent technological advances. Rational approaches to overcoming the bottlenecks in the field are urgently required as membrane proteins, which typically comprise ∼30% of the proteomes of organisms, are dramatically under-represented in the structural database of the Protein Data Bank.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Progress in solving prokaryotic and eukaryotic membrane protein structures.
Figure 2: Strategies for crystallizing membrane proteins.

Similar content being viewed by others

References

  1. Henderson, R. et al. Model for the structure of bacteriorhodopsin based on high-resolution electron cryo-microscopy. J. Mol. Biol. 213, 899–929 (1990).

    CAS  PubMed  Google Scholar 

  2. Cherezov, V. et al. High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science 318, 1258–1265 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Murakami, M. & Kouyama, T. Crystal structure of squid rhodopsin. Nature 453, 363–367 (2008).

    CAS  PubMed  Google Scholar 

  4. Park, J.H., Scheerer, P., Hofmann, K.P., Choe, H.W. & Ernst, O.P. Crystal structure of the ligand-free G-protein-coupled receptor opsin. Nature 454, 183–187 (2008).

    CAS  PubMed  Google Scholar 

  5. Rasmussen, S.G. et al. Crystal structure of the human beta2 adrenergic G-protein-coupled receptor. Nature 450, 383–387 (2007).

    CAS  PubMed  Google Scholar 

  6. Rosenbaum, D.M. et al. GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function. Science 318, 1266–1273 (2007).

    CAS  PubMed  Google Scholar 

  7. Scheerer, P. et al. Crystal structure of opsin in its G-protein-interacting conformation. Nature 455, 497–502 (2008).

    CAS  PubMed  Google Scholar 

  8. Olesen, C. et al. The structural basis of calcium transport by the calcium pump. Nature 450, 1036–1042 (2007).

    CAS  PubMed  Google Scholar 

  9. Shinoda, T., Ogawa, H., Cornelius, F. & Toyoshima, C. Crystal structure of the sodium-potassium pump at 2.4 A resolution. Nature 459, 446–450 (2009).

    CAS  PubMed  Google Scholar 

  10. Faham, S. et al. The crystal structure of a sodium galactose transporter reveals mechanistic insights into Na+/sugar symport. Science 321, 810–814 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Fang, Y. et al. Structure of a prokaryotic virtual proton pump at 3.2 A resolution. Nature 460, 1040–1043 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Gao, X. et al. Structure and mechanism of an amino acid antiporter. Science 324, 1565–1568 (2009).

    CAS  PubMed  Google Scholar 

  13. Ressl, S., Terwisscha van Scheltinga, A.C., Vonrhein, C., Ott, V. & Ziegler, C. Molecular basis of transport and regulation in the Na(+)/betaine symporter BetP. Nature 458, 47–52 (2009).

    CAS  PubMed  Google Scholar 

  14. Shaffer, P.L., Goehring, A., Shankaranarayanan, A. & Gouaux, E. Structure and mechanism of a Na+-independent amino acid transporter. Science 325, 1010–1014 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Shimamura, T. et al. Molecular basis of alternating access membrane transport by the sodium-hydantoin transporter Mhp1. Science 328, 470–473 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Weyand, S. et al. The nucleobase-cation-symport-1 family of membrane transport proteins in Handbook of Metalloproteins (ed. Messerschmidt, A.) (John Wiley, Chichester, 2010).

  17. Weyand, S. et al. The alternating access mechanism of transport as observed in the sodium-hydantoin transporter Mhp1. J. Synchrotron Radiat. 18, 20–23 (2011).

    CAS  PubMed  Google Scholar 

  18. Weyand, S. et al. Structure and molecular mechanism of a nucleobase-cation-symport-1 family transporter. Science 322, 709–713 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Aller, S.G. et al. Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science 323, 1718–1722 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Gerber, S., Comellas-Bigler, M., Goetz, B.A. & Locher, K.P. Structural basis of trans-inhibition in a molybdate/tungstate ABC transporter. Science 321, 246–250 (2008).

    CAS  PubMed  Google Scholar 

  21. Hilf, R.J. & Dutzler, R. Structure of a potentially open state of a proton-activated pentameric ligand-gated ion channel. Nature 457, 115–118 (2009).

    CAS  PubMed  Google Scholar 

  22. Baker, M. Making membrane proteins for structures: a trillion tiny tweaks. Nat. Methods 7, 429–434 (2010).

    CAS  PubMed  Google Scholar 

  23. Bonander, N. et al. Altering the ribosomal subunit ratio in yeast maximizes recombinant protein yield. Microb. Cell Fact. 8, 10 (2009).

    PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Grisshammer, R. & Tate, C. Overexpression of integral membrane proteins for structural studies. Q. Rev. Biophys. 3, 315–422 (1995).

    Google Scholar 

  26. Tate, C.G. Overexpression of mammalian integral membrane proteins for structural studies. FEBS Lett. 504, 94–98 (2001).

    CAS  PubMed  Google Scholar 

  27. Tucker, J. & Grisshammer, R. Purification of a rat neurotensin receptor expressed in Escherichia coli. Biochem. J. 317, 891–899 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Petaja-Repo, U.E., Hogue, M., Laperriere, A., Walker, P. & Bouvier, M. Export from the endoplasmic reticulum represents the limiting step in the maturation and cell surface expression of the human delta opioid receptor. J. Biol. Chem. 275, 13727–13736 (2000).

    CAS  PubMed  Google Scholar 

  29. Ward, C.L. & Kopito, R.R. Intracellular turnover of cystic fibrosis transmembrane conductance regulator. Inefficient processing and rapid degradation of wild-type and mutant proteins. J. Biol. Chem. 269, 25710–25718 (1994).

    CAS  PubMed  Google Scholar 

  30. Sarramegna, V., Talmont, F., Demange, P. & Milon, A. Heterologous expression of G-protein-coupled receptors: comparison of expression systems from the standpoint of large-scale production and purification. Cell. Mol. Life Sci. 60, 1529–1546 (2003).

    CAS  PubMed  Google Scholar 

  31. Tate, C.G., Whiteley, E. & Betenbaugh, M.J. Molecular chaperones stimulate the functional expression of the cocaine-sensitive serotonin transporter. J. Biol. Chem. 274, 17551–17558 (1999).

    CAS  PubMed  Google Scholar 

  32. Higgins, M.K., Demir, M. & Tate, C.G. Calnexin co-expression and the use of weaker promoters increase the expression of correctly assembled Shaker potassium channel in insect cells. Biochim. Biophys. Acta 1610, 124–132 (2003).

    CAS  PubMed  Google Scholar 

  33. Linares, D.M., Geertsma, E.R. & Poolman, B. Evolved Lactococcus lactis strains for enhanced expression of recombinant membrane proteins. J. Mol. Biol. 401, 45–55 (2010).

    CAS  PubMed  Google Scholar 

  34. Wagner, S. et al. Consequences of membrane protein overexpression in Escherichia coli. Mol. Cell. Proteomics 6, 1527–1550 (2007).

    CAS  PubMed  Google Scholar 

  35. Bonander, N. et al. Design of improved membrane protein production experiments: quantitation of the host response. Protein Sci. 14, 1729–1740 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Bonander, N. & Bill, R.M. Relieving the first bottleneck in the drug discovery pipeline: using array technologies to rationalise membrane protein production. Expert Rev. Proteomics 6, 501–505 (2009).

    CAS  PubMed  Google Scholar 

  37. De Schutter, K. et al. Genome sequence of the recombinant protein production host Pichia pastoris. Nat. Biotechnol. 27, 561–566 (2009).

    CAS  PubMed  Google Scholar 

  38. Singh, S. et al. Large-scale functional expression of WT and truncated human adenosine A2A receptor in Pichia pastoris bioreactor cultures. Microb. Cell Fact. 7, 28 (2008).

    PubMed  PubMed Central  Google Scholar 

  39. Mattanovich, D., Gasser, B., Hohenblum, H. & Sauer, M. Stress in recombinant protein producing yeasts. J. Biotechnol. 113, 121–135 (2004).

    CAS  PubMed  Google Scholar 

  40. Ferndahl, C. et al. Increasing cell biomass in Saccharomyces cerevisiae increases recombinant protein yield: the use of a respiratory strain as a microbial cell factory. Microb. Cell Fact. 9, 47 (2010).

    PubMed  PubMed Central  Google Scholar 

  41. Kunji, E.R., Slotboom, D.J. & Poolman, B. Lactococcus lactis as host for overproduction of functional membrane proteins. Biochim. Biophys. Acta 1610, 97–108 (2003).

    CAS  PubMed  Google Scholar 

  42. Surade, S. et al. Comparative analysis and “expression space” coverage of the production of prokaryotic membrane proteins for structural genomics. Protein Sci. 15, 2178–2189 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Geertsma, E.R. & Poolman, B. Production of membrane proteins in Escherichia coli and Lactococcus lactis. Methods Mol. Biol. 601, 17–38 (2010).

    CAS  PubMed  Google Scholar 

  44. Berntsson, R.P. et al. Selenomethionine incorporation in proteins expressed in Lactococcus lactis. Protein Sci. 18, 1121–1127 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Marreddy, R.K. et al. Amino acid accumulation limits the overexpression of proteins in Lactococcus lactis. PLoS ONE 5, e10317 (2010).

    PubMed  PubMed Central  Google Scholar 

  46. Berntsson, R.P. et al. The structural basis for peptide selection by the transport receptor OppA. EMBO J. 28, 1332–1340 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  48. Drew, D. et al. A scalable, GFP-based pipeline for membrane protein overexpression screening and purification. Protein Sci. 14, 2011–2017 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Geertsma, E.R., Groeneveld, M., Slotboom, D.J. & Poolman, B. Quality control of overexpressed membrane proteins. Proc. Natl. Acad. Sci. USA 105, 5722–5727 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Newstead, S., Kim, H., von Heijne, G., Iwata, S. & Drew, D. High-throughput fluorescent-based optimization of eukaryotic membrane protein overexpression and purification in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 104, 13936–13941 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  52. Jacquier, V., Prummer, M., Segura, J.M., Pick, H. & Vogel, H. Visualizing odorant receptor trafficking in living cells down to the single-molecule level. Proc. Natl. Acad. Sci. USA 103, 14325–14330 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Meyer, B.H. et al. FRET imaging reveals that functional neurokinin-1 receptors are monomeric and reside in membrane microdomains of live cells. Proc. Natl. Acad. Sci. USA 103, 2138–2143 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Danelon, C., Terrettaz, S., Guenat, O., Koudelka, M. & Vogel, H. Probing the function of ionotropic and G protein-coupled receptors in surface-confined membranes. Methods 46, 104–115 (2008).

    CAS  PubMed  Google Scholar 

  55. Tate, C.G. Practical considerations of membrane protein instability during purification and crystallisation. Methods Mol. Biol. 601, 187–203 (2010).

    CAS  PubMed  Google Scholar 

  56. Tate, C.G. & Schertler, G.F. Engineering G protein-coupled receptors to facilitate their structure determination. Curr. Opin. Struct. Biol. 19, 386–395 (2009).

    CAS  PubMed  Google Scholar 

  57. Palczewski, K. et al. Crystal structure of rhodopsin: a G protein-coupled receptor. Science 289, 739–745 (2000).

    CAS  PubMed  Google Scholar 

  58. Caffrey, M. & Cherezov, V. Crystallizing membrane proteins using lipidic mesophases. Nat. Protoc. 4, 706–731 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Weiss, H.M. & Grisshammer, R. Purification and characterization of the human adenosine A(2a) receptor functionally expressed in Escherichia coli. Eur. J. Biochem. 269, 82–92 (2002).

    CAS  PubMed  Google Scholar 

  60. Jaakola, V.P. et al. The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist. Science 322, 1211–1217 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Kunji, E.R., Harding, M., Butler, P.J. & Akamine, P. Determination of the molecular mass and dimensions of membrane proteins by size exclusion chromatography. Methods 46, 62–72 (2008).

    CAS  PubMed  Google Scholar 

  62. Lau, F.W., Nauli, S., Zhou, Y. & Bowie, J.U. Changing single side-chains can greatly enhance the resistance of a membrane protein to irreversible inactivation. J. Mol. Biol. 290, 559–564 (1999).

    CAS  PubMed  Google Scholar 

  63. Zhou, Y. & Bowie, J.U. Building a thermostable membrane protein. J. Biol. Chem. 275, 6975–6979 (2000).

    CAS  PubMed  Google Scholar 

  64. Magnani, F., Shibata, Y., Serrano-Vega, M.J. & Tate, C.G. Co-evolving stability and conformational homogeneity of the human adenosine A2a receptor. Proc. Natl. Acad. Sci. USA 105, 10744–10749 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Serrano-Vega, M.J., Magnani, F., Shibata, Y. & Tate, C.G. Conformational thermostabilization of the beta1-adrenergic receptor in a detergent-resistant form. Proc. Natl. Acad. Sci. USA 105, 877–882 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Serrano-Vega, M.J. & Tate, C.G. Transferability of thermostabilizing mutations between beta-adrenergic receptors. Mol. Membr. Biol. 26, 385–396 (2009).

    CAS  PubMed  Google Scholar 

  67. Shibata, Y. et al. Thermostabilization of the neurotensin receptor NTS1. J. Mol. Biol. 390, 262–277 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Warne, T., Serrano-Vega, M.J., Tate, C.G. & Schertler, G.F. Development and crystallization of a minimal thermostabilised G protein-coupled receptor. Protein Expr. Purif. 65, 204–213 (2009).

    CAS  PubMed  Google Scholar 

  69. Hanson, M.A. et al. A specific cholesterol binding site is established by the 2.8 A structure of the human beta2-adrenergic receptor. Structure 16, 897–905 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Wacker, D. et al. Conserved binding mode of human beta2 adrenergic receptor inverse agonists and antagonist revealed by X-ray crystallography. J. Am. Chem. Soc. 132, 11443–11445 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Warne, T. et al. Structure of a beta1-adrenergic G-protein-coupled receptor. Nature 454, 486–491 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Wu, B. et al. Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science 330, 1066–1071 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Chien, E.Y. et al. Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist. Science 330, 1091–1095 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Hirai, T. & Subramaniam, S. Protein conformational changes in the bacteriorhodopsin photocycle: comparison of findings from electron and X-ray crystallographic analyses. PLoS ONE 4, e5769 (2009).

    PubMed  PubMed Central  Google Scholar 

  75. de Groot, B.L., Engel, A. & Grubmuller, H. The structure of the aquaporin-1 water channel: a comparison between cryo-electron microscopy and X-ray crystallography. J. Mol. Biol. 325, 485–493 (2003).

    CAS  PubMed  Google Scholar 

  76. Gautier, A., Mott, H.R., Bostock, M.J., Kirkpatrick, J.P. & Nietlispach, D. Structure determination of the seven-helix transmembrane receptor sensory rhodopsin II by solution NMR spectroscopy. Nat. Struct. Mol. Biol. 17, 768–774 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Neutze, R. et al. Bacteriorhodopsin: a high-resolution structural view of vectorial proton transport. Biochim. Biophys. Acta 1565, 144–167 (2002).

    CAS  PubMed  Google Scholar 

  78. Long, S.B., Campbell, E.B. & Mackinnon, R. Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. Science 309, 897–903 (2005).

    CAS  PubMed  Google Scholar 

  79. Bowler, M.W. et al. Diffraction cartography: applying microbeams to macromolecular crystallography sample evaluation and data collection. Acta Crystallogr. D 66, 855–864 (2010).

    CAS  PubMed  Google Scholar 

  80. Moukhametzianov, R. et al. Protein crystallography with a micrometre-sized synchrotron-radiation beam. Acta Crystallogr. D Biol. Crystallogr. 64, 158–166 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Henrich, B. et al. PILATUS: a single photon counting pixel detector for X-ray applications. Nucl. Instrum. Methods Phys. Res. A 607, 247–249 (2009).

    CAS  Google Scholar 

  82. Neutze, R., Wouts, R., van der Spoel, D., Weckert, E. & Hajdu, J. Potential for biomolecular imaging with femtosecond X-ray pulses. Nature 406, 752–757 (2000).

    CAS  PubMed  Google Scholar 

  83. Iwata, S., Ostermeier, C., Ludwig, B. & Michel, H. Structure at 2.8 A resolution of cytochrome c oxidase from Paracoccus denitrificans. Nature 376, 660–669 (1995).

    CAS  PubMed  Google Scholar 

  84. Ostermeier, C., Iwata, S., Ludwig, B. & Michel, H. Fv fragment-mediated crystallization of the membrane protein bacterial cytochrome c oxidase. Nat. Struct. Biol. 2, 842–846 (1995).

    CAS  PubMed  Google Scholar 

  85. Chaptal, V. et al. Fluorescence Detection of Heavy Atom Labeling (FD-HAL): a rapid method for identifying covalently modified cysteine residues by phasing atoms. J. Struct. Biol. 171, 82–87 (2010).

    CAS  PubMed  Google Scholar 

  86. Roszak, A.W., Gardiner, A.T., Isaacs, N.W. & Cogdell, R.J. Brominated lipids identify lipid binding sites on the surface of the reaction center from Rhodobacter sphaeroides. Biochemistry 46, 2909–2916 (2007).

    CAS  PubMed  Google Scholar 

  87. Schröder, G.F., Levitt, M. & Brunger, A.T. Super-resolution biomolecular crystallography with low-resolution data. Nature 464, 1218–1222 (2010).

    PubMed  PubMed Central  Google Scholar 

  88. Wöhri, A.B. et al. Light-induced structural changes in a photosynthetic reaction center caught by Laue diffraction. Science 328, 630–633 (2010).

    PubMed  Google Scholar 

  89. Andersson, M. et al. Structural dynamics of light-driven proton pumps. Structure 17, 1265–1275 (2009).

    CAS  PubMed  Google Scholar 

  90. Bamber, L., Harding, M., Butler, P.J. & Kunji, E.R. Yeast mitochondrial ADP/ATP carriers are monomeric in detergents. Proc. Natl. Acad. Sci. USA 103, 16224–16229 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank A.D. Cameron for access to information in advance of its publication. This work was supported by the European Membrane Protein Consortium via contract LSHG-CT-2004-504601 (E-MeP) and by the European Drug Initiative on Channels and Transporters via contract HEALTH-F4-2007-201924 (EDICT).

Author information

Authors and Affiliations

  1. School of Life and Health Sciences, Aston University, Birmingham, UK

    Roslyn M Bill

  2. Astbury Centre for Structural Molecular Biology, Institute of Membrane and Systems Biology, University of Leeds, Leeds, UK

    Peter J F Henderson

  3. Division of Molecular Biosciences, Membrane Protein Crystallography Group, Imperial College London, London, UK

    So Iwata

  4. MRC Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge, UK.,

    Edmund R S Kunji

  5. Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, Frankfurt am Main, Germany

    Hartmut Michel

  6. Department of Chemistry, Biochemistry and Biophysics, University of Gothenburg, Gothenburg, Sweden

    Richard Neutze

  7. Department of Biochemistry, University of Oxford, Oxford, UK

    Simon Newstead

  8. Department of Biochemistry, University of Groningen, Groningen, The Netherlands

    Bert Poolman

  9. MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK.,

    Christopher G Tate

  10. Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

    Horst Vogel

Authors
  1. Roslyn M Bill
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter J F Henderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. So Iwata
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Edmund R S Kunji
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hartmut Michel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Richard Neutze
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Simon Newstead
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bert Poolman
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Christopher G Tate
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Horst Vogel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roslyn M Bill.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bill, R., Henderson, P., Iwata, S. et al. Overcoming barriers to membrane protein structure determination. Nat Biotechnol 29, 335–340 (2011). https://doi.org/10.1038/nbt.1833

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nbt.1833

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing