A review of factors affecting the success of membrane protein crystallization using bicelles

Abstract

Several reports have been published detailing various platforms for obtaining crystals of membrane proteins to determine their structure including those that use disk shaped bilayers called bicelles. While these crystals have been readily grown and used for X-ray diffraction, the general understanding as to why bicelles are adequate for such a procedure or how to rationally choose conditions remains unknown. This review intends to discuss issues of protein stabilization and precipitation in the presence of lipids that may influence crystal formation.

Keywords

bicelle / membrane protein / crystallization

References

[1] Afzal S, Tesler W J, Blessing S K, Collins J M, Lis L J (1984). Hydration force between phosphatidylcholine surfaces in aqueous electrolyte solutions. J Colloid Interface Sci, 97(2): 303–307

[2] Angelov B, Ollivon M, Angelova A (1999). X-Ray diffraction study of the effect of the detergent octyl glucoside on the structure of lamellar and nonlamellar lipid/water phases of use for membrane protein reconstitution. Langmuir, 15(23): 8225–8234

[3] Arnold A, Labrot T, Oda R, Dufourc E J (2002). Cation modulation of bicelle size and magnetic alignment as revealed by solid-state NMR and electron microscopy. Biophys J, 83(5): 2667–2680

[4] Bandyopadhyay S, Shelley J C, Klein M L (2001). Molecular dynamics study of the effect of surfactant on a biomembrane. J Phys Chem B, 105(25): 5979–5986

[5] Benz R (1988). Structure and function of porins from gram-negative bacteria. Annu Rev Microbiol, 42(1): 359–393

[6] Bokoch M P, Zou Y, Rasmussen S G F, Liu C W, Nygaard R, Rosenbaum D M (2010). Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor. Nature, 463(7277): 108–112 [10.1038/nature08650]

[7] Boni L T, Stewart T P, Alderfer J L, Hui S W (1981). Lipid-polyethylene glycol interactions: II. formation of defects in bilayers. J Membr Biol, 62(1–2): 71–77

[8] Boni L T, Stewart T P, Hui S W (1984). Alterations in phospholipid polymorphism by polyethylene glycol. J Membr Biol, 80(1): 91–104

[9] Branden C, Tooze J (1999). Introduction to Protein Structure. New York: Garland Publisher

[10] Caffrey M (2003). Membrane protein crystallization. J Struct Biol, 142(1): 108–132

[11] Carion-Taravella B, Lesieur S, Chopineau J, Lesieur P, Ollivon M (2001). Phase behavior of mixed aqueous dispersions of dipalmitoylphosphatidylcholine and dodecyl glycosides: a differential scanning calorimetry and X-ray diffraction investigation. Langmuir, 18(2): 325–335

[12] Carpenter E P, Beis K, Cameron A D, Iwata S (2008). Overcoming the challenges of membrane protein crystallography. Curr Opin Struct Biol, 18(5): 581–586

[13] Cherezov V, Clogston J, Misquitta Y, Abdel-Gawad W, Caffrey M (2002). Membrane protein crystallization in meso: lipid type-tailoring of the cubic phase. Biophys J, 83(6): 3393–3407

[14] Cherezov V, Clogston J, Papiz M Z, Caffrey M (2006). Room to move: crystallizing membrane proteins in swollen lipidic mesophases. J Mol Biol, 357(5): 1605–1618

[15] Cho H S, Dominick J L, Spence M M (2010). Lipid domains in bicelles containing unsaturated lipids and cholesterol. J Phys Chem B, 114(28): 9238–9245

[16] Clarke S (1975). The size and detergent binding of membrane proteins. J Biol Chem, 250(14): 5459–5469

[17] Cunningham B A, Shimotake J E, Tamura-Lis W, Mastran T, Kwok W M, Kauffman J W, Lis L J (1986). The influence of ion species on phosphatidylcholine bilayer structure and packing. Chem Phys Lipids, 39(1–2): 135–143

[18] de Planque M R R, Greathouse D V, Koeppe R E 2nd, Schäfer H, Marsh D, Killian J A (1998). Influence of lipid/peptide hydrophobic mismatch on the thickness of diacylphosphatidylcholine bilayers. A 2H NMR and ESR study using designed transmembrane alpha-helical peptides and gramicidin A. Biochemistry, 37(26): 9333–9345

[19] Diller A, Loudet C, Aussenac F, Raffard G, Fournier S, Laguerre M, Grélard A, Opella S J, Marassi F M, Dufourc E J (2009). Bicelles: a natural ‘molecular goniometer’ for structural, dynamical and topological studies of molecules in membranes. Biochimie, 91(6): 744–751

[20] Dumas F, Sperotto M M, Lebrun M C, Tocanne J F, Mouritsen O G (1997). Molecular sorting of lipids by bacteriorhodopsin in dlpc/dspc lipid bilayers. Biophys J, 73(Oct): 1940–1953

[21] Ericsson C A, Söderman O, Garamus V M, Bergström M, Ulvenlund S (2005). Effects of temperature, salt, and deuterium oxide on the self-aggregation of alkylglycosides in dilute solution. 2. n-Tetradecyl-beta-D-maltoside. Langmuir, 21(4): 1507–1515

[22] Ericsson C A, Söderman O, Garamus V M, Bergström M, Ulvenlund S (2004). Effects of temperature, salt, and deuterium oxide on the self-aggregation of alkylglycosides in dilute solution. 1. n-nonyl-beta-D-glucoside. Langmuir, 20(4): 1401–1408

[23] Faham S (2005). Crystallization of bacteriorhodopsin from bicelle formulations at room temperature. Protein Sci, 14: 836–840 [10.1110/ps.041167605]

[24] Faham S, Boulting G L, Massey E A, Yohannan S, Yang D, Bowie J U (2005). Crystallization of bacteriorhodopsin from bicelle formulations at room temperature. Protein Sci, 14(3): 836–840

[25] Faham S, Bowie J U (2002). Bicelle crystallization: a new method for crystallizing membrane proteins yields a monomeric bacteriorhodopsin structure. J Mol Biol, 316(1): 1–6

[26] Faham S, Ujwal R, Abramson J, Bowie J U (2009). Chapter 5 Practical Aspects of Membrane Proteins Crystallization in Bicelles. In: LarryD. (Ed.), Current Topics in Membranes (Volume 63, pp. 109–125), Academic Press.

[27] Faham S, Yang D, Bare E, Yohannan S, Whitelegge J P, Bowie J U (2004). Side-chain contributions to membrane protein structure and stability. J Mol Biol, 335(1): 297–305

[28] Garavito R M, Picot D (1990). The art of crystallizing membrane proteins. Methods, 1(1): 57–69

[29] Garavito R M, Picot D, Loll P J (1996). Strategies for crystallizing membrane proteins. J Bioenerg Biomembr, 28(1): 13–27

[30] Giordano R, Maisano G, Teixeira J (1997). Sans studies of octyl-β-glucoside and glycine micellar solutions. J Appl Crystallography, 30(2): 761–764

[31] Glaubitz C, Grobner G, Watts A (2000). Structural and orientational information of the membrane embedded M13 coat protein by 13c-mas Nmr spectroscopy. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1463(1): 151–161

[32] Harroun T A, Koslowsky M, Nieh M P, de Lannoy C F, Raghunathan V A, Katsaras J (2005). Comprehensive examination of mesophases formed by DMPC and DHPC mixtures. Langmuir, 21(12): 5356–5361

[33] Hauser H, Paltauf F, Shipley G G (1982). Structure and thermotropic behavior of phosphatidylserine bilayer membranes. Biochemistry, 21(5): 1061–1067

[34] Heerklotz H, Seelig J (2000). Titration calorimetry of surfactant–membrane partitioning and membrane solubilization. Biomembranes, 1508(1–2): 69–85

[35] Helm C A, Tippmann-Krayer P, Möhwald H, Als-Nielsen J, Kjaer K (1991). Phases of phosphatidyl ethanolamine monolayers studied by synchrotron x-ray scattering. Biophys J, 60(6): 1457–1476

[36] Hite R K, Gonen T, Harrison S C, Walz T (2008). Interactions of lipids with aquaporin-0 and other membrane proteins. Pflugers Arch, 456: 651–661 [10.1007/s00424-007-0353-9]

[37] Hite R K, Li Z, Walz T (2010). Principles of membrane protein interactions with annular lipids deduced from aquaporin-0 2d crystals. EMBO J, 29(10): 1652–1658 [10.1038/emboj.2010.68]

[38] Inoko Y, Yamaguchi T, Furuya K, Mitsui T (1975). Effects of cations on dipalmitoyl phosphatidylcholine/cholesterol/water systems. Biochimica et Biophysica Acta (BBA)–Biomembranes, 413(1): 24–32

[39] Jacobson K, Ishihara A, Inman R (1987). Lateral diffusion of proteins in membranes. Annu Rev Physiol, 49(1): 163–175

[40] Jaehnig F, Vogel H, Best L (1982). Unifying description of the effect of membrane proteins on lipid order. vVerification for the melittin/dimyristoylphosphatidylcholine system. Biochem, 21(26): 6790–6798

[41] Jähnig F (1981). Critical effects from lipid-protein interaction in membranes. I. Theoretical description. Biophys J, 36(2): 329–345

[42] Janiak M J, Small D M, Shipley G G (1976). Nature of the Thermal pretransition of synthetic phospholipids: dimyristolyl- and dipalmitoyllecithin. Biochemistry, 15(21): 4575–4580

[43] Johnson S J, Bayerl T M, Weihan W, Noack H, Penfold J, Thomas R K, Kanellas D, Rennie A R, Sackmann E (1991). Coupling of spectrin and polylysine to phospholipid monolayers studied by specular reflection of neutrons. Biophys J, 60(5): 1017–1025

[44] Kam Z, Shore H B, Feher G (1978). On the crystallization of proteins. J Mol Biol, 123(4): 539–555

[45] Keller M, Kerth A, Blume A (1997). Thermodynamics of interaction of octyl glucoside with phosphatidylcholine vesicles: partitioning and solubilization as studied by high sensitivity titration calorimetry. Biomembranes, 1326(2): 178–192

[46] Kilic M S, Bazant M Z, Ajdari A (2007). Steric effects in the dynamics of electrolytes at large applied voltages. I. Double-layer charging. Phys Rev E Stat Nonlin Soft Matter Phys, 75(2): 021502

[47] Killian J A (1998). Hydrophobic mismatch between proteins and lipids in membranes. Biochimica et Biophysica Acta (BBA)–Biomembranes, 1376(3): 401–415

[48] Kimble-Hill A C, Singh D, Laible P D, Hanson D K, Porcar L, Butler P, Perez-Salas U (2009). Detergent localization in model proteo-bicelles. Biophys J, 96(3): 453a

[49] Koehorst R B M, Spruijt R B, Vergeldt F J, Hemminga M A (2004). Lipid bilayer topology of the transmembrane alpha-helix of M13 Major coat protein and bilayer polarity profile by site-directed fluorescence spectroscopy. Biophys J, 87(3): 1445–1455

[50] Kuhl T, Guo Y, Alderfer J L, Berman A D, Leckband D, Israelachvili J, Hui S W (1996). Direct measurement of polyethylene glycol induced depletion attraction between lipid bilayers. Langmuir, 12(12): 3003–3014

[51] Kühlbrandt W, Auer M, Scarborough G A (1998). Structure of the P-type ATPases. Curr Opin Struct Biol, 8(4): 510–516

[52] Kwan C C, Rosen M (1978). The relationship of structure to properties in surfactants: VII. synthesis and properties of some sodium 1,4-and 2,6-alkoxynaphthalenesulfonates. Journal of the American Oil Chemists' Society, 55(8): 625–628

[53] Lambert O, Levy D, Ranck J L, Leblanc G, Rigaud J L (1998). A new “gel-like” phase in dodecyl maltoside-lipid mixtures: implications in solubilization and reconstitution studies. Biophys J, 74(2 Pt 1): 918–930

[54] Landau E M, Rosenbusch J P (1996). Lipidic cubic phases: a novel concept for the crystallization of membrane proteins. Proc Natl Acad Sci USA, 93(25): 14532–14535

[55] Lee A G (2004). How lipids affect the activities of integral membrane proteins. Biochim Biophys Acta, 1666: 62–87 [10.1016/j.bbamem.2004.05.012]

[56] Lis L J, Lis W T, Parsegian V A, Rand R P (1981a). Adsorption of divalent cations to a variety of phosphatidylcholine bilayers. Biochemistry, 20(7): 1771–1777

[57] Lis L J, Parsegian V A, Rand R P (1981b). Binding of divalent cations of dipalmitoylphosphatidylcholine bilayers and its effect on bilayer interaction. Biochemistry, 20(7): 1761–1770

[58] Liu F, Lewis R N H, Hodges R S, Mcelhaney R N (2002). Effect of variations in the structure of a polyleucine-based α-helical transmembrane peptide on its interaction with phosphatidylcholine bilayers. Biochem, 41(29): 9197–9207

[59] Lodish H, Berk A, Matsudaira P, Kaiser C, Krieger M, Scott M (2004). Molecular Cell Biology (5th Ed.). New York: Freeman Press

[60] Lookman T, Pink D A, Grundke E W, Zuckermann M J, deVerteuil F (1982). Phase separation in lipid bilayers containing integral proteins. Computer simulation studies. Biochemistry, 21(22): 5593–5601

[61] Loosley-Millman M E, Rand R P, Parsegian V A (1982). Effects of monovalent ion binding and screening on measured electrostatic forces between charged phospholipid bilayers. Biophys J, 40(3): 221–232

[62] Luecke H, Schobert B, Stagno J, Imasheva E S, Wang J M, Balashov S P, Lanyi J K (2008). Crystallographic structure of xanthorhodopsin, the light-driven proton pump with a dual chromophore. Proc Natl Acad Sci USA, 105(43): 16561–16565

[63] MacDonald A L, Pink D A (1987). Thermodynamics of glycophorin in phospholipid bilayer membranes. Biochemistry, 26(7): 1909–1917

[64] McLaughlin S (1989). The electrostatic properties of membranes. Annu Rev Biophys Biophys Chem, 18(1): 113–136

[65] Mcpherson A (1991). Useful Principles for the Crystallization of Proteins. Boca Raton: CRC Press

[66] Michel H, Oesterhelt D (1980). Three-dimensional crystals of membrane proteins: bacteriorhodopsin. Proc Natl Acad Sci USA, 77(3): 1283–1285

[67] Mitchell D J, Tiddy G J T, Waring L, Bostock T, Mcdonald M P (1983). Phase behaviour of polyoxyethylene surfactants with water. mesophase structures and partial miscibility (cloud points). Journal of the Chemical Society, Faraday Transactions 1. Physical Chemistry in Condensed Phases, 79(4): 975–1000

[68] Mouritsen O G, Bloom M (1984). Mattress model of lipid-protein interactions in membranes. Biophys J, 46(2): 141–153

[69] Mouritsen O G, Bloom M (1993). Models of lipid-protein interactions in membranes. Annu Rev Biophys Biomol Struct, 22: 145–171

[70] Needham D, McIntosh T J, Evans E (1988). Thermomechanical and transition properties of dimyristoylphosphatidylcholine/cholesterol bilayers. Biochemistry, 27(13): 4668–4673

[71] Nieh M P, Glinka C J, Krueger S, Prosser R S, Katsaras J (2002). SANS study on the effect of lanthanide ions and charged lipids on the morphology of phospholipid mixtures. Small-angle neutron scattering. Biophys J, 82(5): 2487–2498

[72] Nilsson F, Söderman O, Johansson I (1996). Physical–chemical properties of the N-octyl B-D-glucoside/water system. a phase dDiagram, self-diffusion Nmr, and saxs study. Langmuir, 12(4): 902–908

[73] Nollert P (2004). Lipidic cubic phases as matrices for membrane protein crystallization. Methods, 34(3): 348–353

[74] Owicki J C, Springgate M W, McConnell H M (1978). Theoretical study of protein—lipid interactions in bilayer membranes. Proc Natl Acad Sci USA, 75(4): 1616–1619

[75] Pebay-Peyroula E, Garavito R M, Rosenbusch J P, Zulauf M, Timmins P A (1995). Detergent structure in tetragonal crystals of OmpF porin. Structure, 3(10): 1051–1059

[76] Petrache H I, Tristram-Nagle S, Harries D, Kučerka N, Nagle J F, Parsegian V A (2006). Swelling of phospholipids by monovalent salt. J Lipid Res, 47(2): 302–309

[77] Pink D A, Chapman D (1979). Protein-lipid interactions in bilayer membranes: a lattice model. Proc Natl Acad Sci USA, 76(4): 1542–1546

[78] Pink D A, Green T J, Chapman D (1980). Raman scattering in bilayers of saturated phosphatidylcholines. Experiment and theory. Biochemistry, 19(2): 349–356

[79] Raffard G, Steinbruckner S, Arnold A, Davis J H, Dufourc E J (2000). Temperature–composition diagram of dimyristoylphosphatidylcho-line–dicaproylphosphatidylcholine “bicelles” self-orienting in the magnetic field. a solid state 2h and 31p Nmr study. Langmuir, 16(20): 7655–7662

[80] Rasmussen S G F, Choi H-J, Rosenbaum D M, Kobilka T S, Thian F S, Edwards P C (2007). Crystal structure of the human [Bgr]2 adrenergic g-Protein-coupled receptor. Nature, 450(7168): 383– 387

[81] Roth M, Lewit-Bentley A, Michel H, Deisenhofer J, Huber R, Oesterhelt D (1989). Detergent structure in crystals of a bacterial photosynthetic reaction centre. Nature, 340(6235): 659–662

[82] Sabra M C, Mouritsen O G (1998). Steady-state compartmentalization of lipid membranes by active proteins. Biophys J, 74(2 Pt 1): 745–752

[83] Santonicola M G L, Lenhoff A M, Kaler E W (2008). Binding of alkyl polyglucoside surfactants to bacteriorhodopsin and its relation to protein stability. Biophys J, 94(9): 3647–3658

[84] Seelig A, Seelig J (1977). Effect of a single cis double bond on the structures of a phospholipid bilayer. Biochemistry, 16(1): 45–50

[85] Sharpe S, Barber K R, Grant C W M, Goodyear D, Morrow M R (2002). Organization of model helical peptides in lipid bilayers: insight into the behavior of single-span protein transmembrane domains. Biophys J, 83(1): 345–358

[86] Stewart T P, Hui S W, Portis A R Jr, Papahadjopoulos D (1979). Complex Phase Mixing of Phosphatidylcholine and phosphatidylserine in multilamellar membrane vesicles. Biochimica et Biophysica Acta (BBA)–Biomembranes, 556(1): 1–16

[87] Strandberg E, Ozdirekcan S, Rijkers D T S, van der Wel P C A, Koeppe R E 2nd, Liskamp R M, Killian J A (2004). Tilt angles of transmembrane model peptides in oriented and non-oriented lipid bilayers as determined by 2H solid-state NMR. Biophys J, 86(6): 3709–3721

[88] Sukumaran S, Hauser K, Maier E, Benz R, Mäntele W (2006). Structure-function correlation of outer membrane protein porin from Paracoccus denitrificans. Biopolymers, 82(4): 344–348

[89] Takeda K, Sato H, Hino T, Kono M, Fukuda K, Sakurai I, Okada T, Kouyama T (1998). A novel three-dimensional crystal of bacteriorhodopsin obtained by successive fusion of the vesicular assemblies. J Mol Biol, 283(2): 463–474

[90] Tamm I, Kikuchi T (1979). Early termination of heterogeneous nuclear RNA transcripts in mammalian cells: accentuation by 5,6-dichloro 1-beta-D-ribofuranosylbenzimidazole. Proc Natl Acad Sci USA, 76(11): 5750–5754

[91] Tamura-Lis W, Reber E J, Cunningham B A, Collins J M, Lis L J (1986). Ca²⁺ induced phase separations in phospholipid mixtures. Chem Phys Lipids, 39(1-2): 119–124

[92] Tatulian S A (1983). Effect of lipid phase transition on the binding of anions to dimyristoylphosphatidylcholine liposomes. Biochimica et Biophysica Acta (BBA)–Biomembranes, 736(2): 189–195

[93] Tessier-Lavigne M, Boothroyd A, Zuckermann M J, Pink D A (1982). Lipid-mediated interactions between intrinsic molecules in bilayer membranes. J Chem Phys, 76(9): 4587–4599

[94] Tilcock C P, Fisher D (1979). Interaction of phospholipid membranes with poly(ethylene glycol)s. Biochim Biophys Acta, 557(1): 53–61

[95] Träuble H, Eibl H (1974). Electrostatic effects on lipid phase transitions: membrane structure and ionic environment. Proc Natl Acad Sci USA, 71(1): 214–219

[96] Ujwal R, Bowie J U (2011). Crystallizing membrane proteins using lipidic bicelles. Methods, 55(4): 337–341

[97] Ujwal R, Cascio D, Colletier J P, Faham S, Zhang J, Toro L, Ping P, Abramson J (2008). The crystal structure of mouse VDAC1 at 2.3 A resolution reveals mechanistic insights into metabolite gating. Proc Natl Acad Sci USA, 105(46): 17742–17747

[98] van Dam L, Karlsson G, Edwards K (2004). Direct Observation and Characterization of Dmpc/Dhpc Aggregates under Conditions Relevant for Biological Solution Nmr. Biochimica et Biophysica Acta (BBA)–Biomembranes, 1664(2): 241–256

[99] van der Wel P C A, Strandberg E, Killian J A, Koeppe R E 2nd (2002). Geometry and intrinsic tilt of a tryptophan-anchored transmembrane alpha-helix determined by (2)H NMR. Biophys J, 83(3): 1479–1488

[100] Venturoli M, Smit B, Sperotto M M (2005). Simulation studies of protein-induced bilayer deformations, and lipid-induced protein tilting, on a mesoscopic model for lipid bilayers with embedded proteins. Biophys J, 88(3): 1778–1798

[101] Vinothkumar K R (2011). Structure of rhomboid protease in a lipid environment. J Mol Biol, 407(2): 232–247

[102] Vinson P K, Talmon Y, Walter A (1989). Vesicle-micelle transition of phosphatidylcholine and octyl glucoside elucidated by cryo-transmission electron microscopy. Biophys J, 56(4): 669–681

[103] Yamazaki M, Ito T (1990). Deformation and instability in membrane structure of phospholipid vesicles caused by osmophobic association: mechanical stress model for the mechanism of poly(ethylene glycol)-induced membrane fusion. Biochemistry, 29(5): 1309–1314

[104] Zhang Y P, Lewis R N H, McElhaney R N (1997). Calorimetric and spectroscopic studies of the thermotropic phase behavior of the n-saturated 1,2-diacylphosphatidylglycerols. Biophys J, 72(2 Pt 1): 779–793

RIGHTS & PERMISSIONS

Higher Education Press and Springer-Verlag Berlin Heidelberg