Skip to main content

Thank you for visiting 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.

Maltose–neopentyl glycol (MNG) amphiphiles for solubilization, stabilization and crystallization of membrane proteins

This article has been updated


The understanding of integral membrane protein (IMP) structure and function is hampered by the difficulty of handling these proteins. Aqueous solubilization, necessary for many types of biophysical analysis, generally requires a detergent to shield the large lipophilic surfaces of native IMPs. Many proteins remain difficult to study owing to a lack of suitable detergents. We introduce a class of amphiphiles, each built around a central quaternary carbon atom derived from neopentyl glycol, with hydrophilic groups derived from maltose. Representatives of this maltose–neopentyl glycol (MNG) amphiphile family show favorable behavior relative to conventional detergents, as manifested in multiple membrane protein systems, leading to enhanced structural stability and successful crystallization. MNG amphiphiles are promising tools for membrane protein science because of the ease with which they may be prepared and the facility with which their structures may be varied.

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type



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

Figure 1: Chemical structures of MNG amphiphiles (MNG-1, MNG-2 and MNG-3) and their linear counterparts (MPA-1, MPA-2, MPA-3, MPA-4, DM, UDM, DDM and TDM).
Figure 2: GPCR stability in MNG amphiphiles or conventional detergents.
Figure 3: SDS-12% PAGE analysis and western blot detection of MelB.
Figure 4: Stability of SQR solubilized with MNG amphiphiles or conventional detergents.
Figure 5: Long-term stability of LeuT and R. capsulatus superassembly in MNG amphiphiles or conventional detergents.
Figure 6: Image and X-ray diffraction pattern from crystals of cytochrome b6f–MNG-3 complexes.

Change history

  • 09 November 2010

    In the version of this article initially published online, Figure 1 contained errors (an incorrect number of carbons were drawn in the molecules). The error has been corrected for the print, PDF and HTML versions of this article.


  1. Liu, J. & Rost, B. Comparing function and structure between entire proteomes. Protein Sci. 10, 1970–1979 (2001).

    Article  CAS  Google Scholar 

  2. Lacapère, J.J., Pebay-Peyroula, E., Neumann, J.M. & Etchebest, C. Determining membrane protein structures: still a challenge! Trends Biochem. Sci. 32, 259–270 (2007).

    Article  Google Scholar 

  3. Privé, G.G. Detergents for the stabilization and crystallization of membrane proteins. Methods 41, 388–397 (2007).

    Article  Google Scholar 

  4. Schafmeister, C.E., Meircke, L.J.W. & Stroud, R.M. Structure at 2.5 Å of a designed peptide that maintains solubility of membrane proteins. Science 262, 734–738 (1993).

    Article  CAS  Google Scholar 

  5. McGregor, C.-L. et al. Lipopeptide detergents designed for the structural study of membrane protein. Nat. Biotechnol. 21, 171–176 (2003).

    Article  CAS  Google Scholar 

  6. Zhao, X. et al. Designer short peptide surfactants stabilize G protein-coupled receptor bovine rhodopsin. Proc. Natl. Acad. Sci. USA 103, 17707–17712 (2006).

    Article  CAS  Google Scholar 

  7. Tribet, C., Audebert, R. & Popot, J.-L. Amphipols: polymers that keep membrane proteins soluble in aqueous solutions. Proc. Natl. Acad. Sci. USA 93, 15047–15050 (1996).

    Article  CAS  Google Scholar 

  8. Popot, J.-L. Amphipols, nanodiscs, and fluorinated surfactants: three non-conventional approaches to studying membrane proteins in aqueous solutions. Annu. Rev. Biochem. 79, 737–775 (2010).

    Article  CAS  Google Scholar 

  9. Nath, A., Atkins, W.M. & Sligar, S.G. Applications of phospholipid bilayer nanodiscs in the study of membranes and membrane proteins. Biochemistry 46, 2059–2069 (2007).

    Article  CAS  Google Scholar 

  10. Borch, J. & Hamann, T. The nanodisc: a novel tool for membrane protein studies. Biol. Chem. 390, 805–814 (2009).

    Article  CAS  Google Scholar 

  11. Breyton, C. et al. Micellar and biochemical properties of (hemi)fluorinated surfactants are controlled by the size of the polar head. Biophys. J. 97, 1077–1086 (2009).

    Article  CAS  Google Scholar 

  12. Zhang, Q. et al. Designing facial amphiphiles for the stabilization of integral membrane protein. Angew. Chem. Int. Edn. 119, 7153–7155 (2007).

    Article  Google Scholar 

  13. Hoffmann, R.W. Flexible molecules with defined shape-conformational design. Angew. Chem. Int. Edn. Engl. 31, 1124–1134 (1992).

    Article  Google Scholar 

  14. McQuade, D.T. et al. Rigid amphiphiles for membrane protein manipulation. Angew. Chem. Int. Edn. 39, 758–761 (2000).

    Article  CAS  Google Scholar 

  15. Chae, P.S., Wander, M.J., Bowling, A.P., Laible, P.D. & Gellman, S.H. Glycotripod amphiphiles for solubilization and stabilization of a membrane protein superassembly: importance of branching in the hydrophilic portion. ChemBioChem 9, 1706–1709 (2008).

    Article  CAS  Google Scholar 

  16. Rosenbaum, D.M. et al. GPCR engineering yields high-resolution structural insights into β2-adrenergic receptor function. Science 318, 1266–1273 (2007).

    Article  CAS  Google Scholar 

  17. Bassilana, M., Pourcher, T. & Lablanc, G. Melibiose permease of Escherichia coli . J. Biol. Chem. 263, 9663–9667 (1988).

    CAS  PubMed  Google Scholar 

  18. Alexandrov, A.I., Mileni, M., Chien, E.Y., Hanson, M.A. & Stevens, R.C. Microscale fluorescent thermal stability assay for membrane proteins. Structure 16, 351–359 (2008).

    Article  CAS  Google Scholar 

  19. Horsefield, R., Iwata, S. & Byrne, B. Complex II from a structural perspective. Curr. Protein Pept. Sci. 5, 107–118 (2004).

    Article  CAS  Google Scholar 

  20. Puustinen, A., Finel, M., Haltia, T., Gennis, R.B. & Wikström, M. Properties of the two terminal oxidases of Escherichia coli . Biochemistry 30, 3936–3942 (1991).

    Article  CAS  Google Scholar 

  21. 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).

    Article  CAS  Google Scholar 

  22. Deckert, G. et al. The complete genome of the hyperthermophilic bacterium Aquifex aeolicus . Nature 392, 353–358 (1998).

    Article  CAS  Google Scholar 

  23. Yamashita, A., Singh, S.K., Kawate, T., Jin, Y. & Gouaux, E. Crystal structure of a bacterial homologue of Na+/Cl-dependent neurotransmitter transporters. Nature 437, 215–223 (2005).

    Article  CAS  Google Scholar 

  24. Quick, M. & Javitch, J.A. Monitoring the function of membrane transport proteins in detergent-solubilized form. Proc. Natl. Acad. Sci. USA 104, 3603–3608 (2007).

    Article  CAS  Google Scholar 

  25. Hu, X.C., Ritz, T., Damjanovic, A., Authenrieth, F. & Schulten, K. Photosynthetic apparatus of purple bacteria. Q. Rev. Biophys. 35, 1–62 (2002).

    Article  CAS  Google Scholar 

  26. Youvan, D.C., Ismail, S. & Bylina, E.J. Chromosomal deletion and plasmid complementation of the photosynthetic reaction center and light-harvesting genes from Rhodopseudomonas capsulata . Gene 38, 19–30 (1985).

    Article  CAS  Google Scholar 

  27. Stroebel, D., Choquet, Y., Popot, J.-L. & Picot, D. An atypical haem in the cytochrome b 6 f complex. Nature 426, 413–418 (2003).

    Article  CAS  Google Scholar 

  28. Rosenbaum, D.M., Rasmussen, S.G.F. & Kobilka, B.K. The structure and function of G-protein-coupled receptors. Nature 459, 356–363 (2009).

    Article  CAS  Google Scholar 

  29. Cherezov, V. et al. High-resolution crystal structure of an engineered human β2-adrenergic G protein-coupled receptor. Science 318, 1258–1265 (2007).

    Article  CAS  Google Scholar 

  30. Hanson, M.A. et al. A specific cholesterol binding site is established by the 2.8 Å structure of the human β2-adrenergic receptor. Structure 16, 897–905 (2008).

    Article  CAS  Google Scholar 

  31. Sanders, C.R. & Sonnichsen, F. Solution NMR of membrane proteins: practice and challenges. Magn. Reson. Chem. 44, S24–S40 (2006).

    Article  CAS  Google Scholar 

  32. Barrera, N.P., Di Bartolo, N., Booth, P.J. & Robinson, C.V. Micelles protect membrane complexes from solution to vacuum. Science 321, 243–246 (2008).

    Article  CAS  Google Scholar 

  33. Li, L. et al. Simple host-guest chemistry to modulate the process of concentration and crystallization of membrane proteins by detergent capture in a microfluidic device. J. Am. Chem. Soc. 130, 14324–14328 (2008).

    Article  CAS  Google Scholar 

  34. Pourcher, T., Leclercq, S., Brandolin, G. & Leblanc, G. Melibiose permease of Escherichia coli: large scale purification and evidence that H+, Na+, and Li+ sugar symport is catalyzed by a single polypeptide. Biochemistry 34, 4412–4420 (1995).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  37. Kabsch, W. Automatic processing of rotation diffraction data from crystals of initially unknown symmetry and cell constants. J. Appl. Crystallogr. 26, 795–800 (1993).

    Article  CAS  Google Scholar 

  38. Collaborative Computational Project. Number 4. The CCP4 Suite: Programs for Protein Crystallography. Acta Crystallogr. D50, 760–763 (1994).

  39. Adams, P.D. et al. PHENIX: building new software for automated crystallographic structure determination. Acta Crystallogr. D Biol. Crystallogr. 58, 1948–1954 (2002).

    Article  Google Scholar 

  40. Bricogne, G. et al. BUSTER, version 2.8.0. (Global Phasing Ltd., Cambridge, UK, 2009).

  41. Pierre, Y., Breyton, C., Kramers, D. & Popot, J.-L. Purification and characterization of the cytochrome b 6 f complex from Chlamydomonas reinhardtii . J. Biol. Chem. 270, 29342–29349 (1995).

    Article  CAS  Google Scholar 

  42. Goren, M.A. & Fox, B.G. Wheat germ cell-free translation, purification, and assembly of a functional human stearoyl-CoA desaturase complex. Protein Expr. Purif. 62, 171–178 (2008).

    Article  CAS  Google Scholar 

Download references


This work was supported by US National Institutes of Health (NIH) grant P01 GM75913 (S.H.G.), NS28471 (B.K.), by the Lundbeck Foundation (S.G.F.R., C.J.L. and U.G.), by the Danish National Research Council (C.J.L., U.G.), by the European Community's Seventh Framework Programme FP7/2007-2013 under grant agreement no. HEALTH-F4-2007-201924, EDICT Consortium (K.G., U.G. and B.B.) and by NIH grant GM083118 and NIH Protein Structure Initiative grants U54 GM-074901 (J.L. Markley, PI; B.G.F.) and U54 GM094584 (B.G.F.). This work was also supported by grant no. R21HL087895 from the US National Heart, Lung, and Blood Institute, by the Texas Norman Hackerman Advanced Research Program under grant no. 010674-0034-2009 (to L.G.) and by the Center for Membrane Protein Research, Texas Tech University Health Sciences Center. R.R.R. was funded by the Defence Science and Technology Laboratory. We thank P. Laible (Argonne National Laboratory, Chicago) for supplying membrane preparations from R. capsulatus. We acknowledge SOLEIL (Saint-Aubin, France) for provision of synchrotron radiation facilities, and we would like to thank B. Guimaraes for assistance in using the beamline Proxima 1. We also thank R. Kaback (University of California, Los Angeles) and G. Leblanc (Institut de Biologie et Technologies–Saclay) for the MelB expression system. M.A.G. acknowledges support from the US National Science Foundation East Asia and Pacific Summer Institutes Fellowship program. We thank G. Cecchini (University of California, San Francisco) and J. Ruprecht (Medical Research Council Mitochondrial Biology Unit, Cambridge) for the purified SQR and the details of the SQR functional assay, and we acknowledge the assistance of P. Nixon in the analysis of the SQR functional data.

Author information

Authors and Affiliations



P.S.C. designed the MNG amphiphiles, with contributions from S.G.F.R., B.K. and S.H.G. P.S.C. synthesized the amphiphiles. P.S.C., S.G.F.R., R.R.R., K.G., R.C., M.A.G., A.C.K., S.N., Y.P. and D.P. designed and performed the research and interpreted the data. C.J.L., D.D., B.G.F., L.G., U.G., J.-L.P., B.B., B.K. and S.H.G. contributed to experimental design and data interpretation. P.S.C. and S.H.G. wrote the manuscript, with oversight from S.G.F.R., R.R.R., K.G., R.C., M.A.G., A.C.K., S.N., C.J.L., Y.P., D.D., J.-L.P., D.P., B.G.F., L.G., U.G., B.B. and B.K.

Corresponding authors

Correspondence to Bernadette Byrne, Brian Kobilka or Samuel H Gellman.

Ethics declarations

Competing interests

P.S.C, S.G.F.R., B.K. and S.H.G. are co-inventors on a patent application that covers the MNG amphiphiles.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–9, Supplementary Tables 1 and 2, and Supplementary Note (PDF 864 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Chae, P., Rasmussen, S., Rana, R. et al. Maltose–neopentyl glycol (MNG) amphiphiles for solubilization, stabilization and crystallization of membrane proteins. Nat Methods 7, 1003–1008 (2010).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


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