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Lipid Cubic Phase for Membrane Protein X-ray Crystallography

  • Jialu Zha
  • Dianfan Li
Chapter

Abstract

Membrane proteins constitute an integral part of biomembrane and play key roles in fundamental biological and physiological processes such as metabolism, signaling, and ion homeostasis. About half of all drug targets are membrane proteins. Elucidation of three-dimensional structures of membrane proteins by X-ray crystallography can provide mechanistic insights for their cellular activity and reveal atomic resolution of architectural details for rational design of novel therapeutics. However, the pace of IMP crystallography has been relatively slow due to great challenges in crystallization. Lipid cubic phase (LCP) has proven to be promising in tackling the crystallization problem by providing a membrane-alike environment. Its bilayer is composed of neutral lipids, such as monoacylglycerols, and can accommodate a substantial amount of native lipids such as phospholipids and cholesterol. Thus, the structure and composition of LCP mimic biomembranes and therefore offer a native-like environment for membrane proteins, which is favorable for functionality and crystallization. Here, the principles for LCP formation, membrane protein reconstitution, and crystallization process are described. The successful application of LCP crystallization for a wide range of membrane proteins including receptors, complexes, transporters, channels, enzymes, membrane protein insertion chaperons, and outer membrane β-barrels is summarized. General methods and protocols for this method are also described.

Notes

Acknowledgements

This work was supported by the 1000 Young Talent Program, the Shanghai Pujiang Talent Program (15PJ1409400), the National Natural Science Foundation of China (No. 31570748 and U1632127), the CAS Shanghai Science Research Center (CAS-SSRC-YJ-2015-02), and Key Program of CAS Frontier Science (QYZDB-SSW-SMC037).

References

  1. 1.
    Yildirim MA, Goh KI, Cusick ME, Barabasi AL, Vidal M (2007) Drug-target network. Nat Biotechnol 25(10):1119–1126CrossRefGoogle Scholar
  2. 2.
    Waseda Y, Matsubara E, Shinoda K (2011) X-ray diffraction crystallography: introduction, examples and solved problems. Springer Science & Business MediaGoogle Scholar
  3. 3.
    Rupp B (2009) Biomolecular crystallography: principles, practice, and application to structural biologyGoogle Scholar
  4. 4.
    Carpenter EP, Beis K, Cameron AD, Iwata S (2008) Overcoming the challenges of membrane protein crystallography. Curr Opin Struct Biol 18(5):581–586CrossRefGoogle Scholar
  5. 5.
    Parker JL, Newstead S (2016) Membrane protein crystallization: current trends and future perspectives. Adv Exp Med Biol 922:61–72CrossRefGoogle Scholar
  6. 6.
    Kloppmann E, Punta M, Rost B (2012) Structural genomics plucks high-hanging membrane proteins. Curr Opin Struct Biol 22(3):326–332CrossRefGoogle Scholar
  7. 7.
    Caffrey M, Li D, Dukkipati A (2012) Membrane protein structure determination using crystallography and lipidic mesophases: recent advances and successes. Biochemistry 51(32):6266–6288CrossRefGoogle Scholar
  8. 8.
    Privé GG (2007) Detergents for the stabilization and crystallization of membrane proteins. Methods 41(4):388–397CrossRefGoogle Scholar
  9. 9.
    Loll P (2014) Membrane proteins, detergents and crystals: what is the state of the art? Acta Crystallogr F 70(12):1576–1583CrossRefGoogle Scholar
  10. 10.
    Cao Y, Jin X, Huang H, Derebe MG, Levin EJ, Kabaleeswaran V, Pan Y, Punta M, Love J, Weng J, Quick M, Ye S, Kloss B, Bruni R, Martinez-Hackert E, Hendrickson WA, Rost B, Javitch JA, Rajashankar KR, Jiang Y, Zhou M (2011) Crystal structure of a potassium ion transporter. TrkH. Nature 471(7338):336–340CrossRefGoogle Scholar
  11. 11.
    Mancia F, Love J (2010) High-throughput expression and purification of membrane proteins. J Struct Biol 172(1):85–93CrossRefGoogle Scholar
  12. 12.
    Abdul-Hussein S, Andrell J, Tate CG (2013) Thermostabilisation of the serotonin transporter in a cocaine-bound conformation. J Mol Biol 425(12):2198–2207CrossRefGoogle Scholar
  13. 13.
    Magnani F, Serrano-Vega MJ, Shibata Y, Abdul-Hussein S, Lebon G, Miller-Gallacher J, Singhal A, Strege A, Thomas JA, Tate CG (2016) A mutagenesis and screening strategy to generate optimally thermostabilized membrane proteins for structural studies. Nat Protoc 11(8):1554–1571CrossRefGoogle Scholar
  14. 14.
    Coleman JA, Green EM, Gouaux E (2016) X-ray structures and mechanism of the human serotonin transporter. Nature 532(7599):334–339CrossRefGoogle Scholar
  15. 15.
    Lebon G, Bennett K, Jazayeri A, Tate CG (2011) Thermostabilisation of an agonist-bound conformation of the human adenosine A(2A) receptor. J Mol Biol 409(3):298–310CrossRefGoogle Scholar
  16. 16.
    Doré AS, Robertson N, Errey JC, Ng I, Hollenstein K, Tehan B, Hurrell E, Bennett K, Congreve M, Magnani F, Tate CG, Weir M, Marshall FH (2011) Structure of the adenosine A(2A) receptor in complex with ZM241385 and the xanthines XAC and caffeine. Structure 19(9):1283–1293CrossRefGoogle Scholar
  17. 17.
    Carpenter B, Nehmé R, Warne T, Leslie AGW, Tate CG (2016) Structure of the adenosine A(2A) receptor bound to an engineered G protein. Nature 536(7614):104–107CrossRefGoogle Scholar
  18. 18.
    Miller JL, Tate CG (2011) Engineering an ultra-thermostable β(1)-adrenoceptor. J Mol Biol 413(3):628–638.Google Scholar
  19. 19.
    Carpenter B, Tate CG (2016) Engineering a minimal G protein to facilitate crystallisation of G protein-coupled receptors in their active conformation. Protein Eng Des Sel 29(12):583–594Google Scholar
  20. 20.
    Miller-Gallacher JL, Nehmé R, Warne T, Edwards PC, Schertler GFX, Leslie AGW, Tate CG (2014) The 2.1 Å resolution structure of cyanopindolol-bound β(1)-Adrenoceptor identifies an intramembrane Na(+) ion that stabilises the ligand-free receptor. PLoS One 9(3):e92727CrossRefGoogle Scholar
  21. 21.
    Carpenter B, Nehmé R, Warne T, Leslie AGW, Tate CG (2016) Structure of the adenosine A2A receptor bound to an engineered G protein. Nature 536(7614):104–107CrossRefGoogle Scholar
  22. 22.
    Faham S, Bowie JU (2002) Bicelle crystallization: a new method for crystallizing membrane proteins yields a monomeric bacteriorhodopsin structure. J Mol Biol 316(1):1–6CrossRefGoogle Scholar
  23. 23.
    Sanders CR, Prosser RS (1998) Bicelles: a model membrane system for all seasons? Structure 6(10):1227–1234CrossRefGoogle Scholar
  24. 24.
    Qiu H, Caffrey M (2000) The phase diagram of the monoolein/water system: metastability and equilibrium aspects. Biomaterials 21(3):223–234CrossRefGoogle Scholar
  25. 25.
    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):3393–3407CrossRefGoogle Scholar
  26. 26.
    Landau EM, Rosenbusch JP (1996) Lipidic cubic phases: a novel concept for the crystallization of membrane proteins. Proc Natl Acad Sci U S A 93(25):14532–14535CrossRefGoogle Scholar
  27. 27.
    Pebay-Peyroula E, Rummel G, Rosenbusch JP, Landau EM (1997) X-ray structure of bacteriorhodopsin at 2.5 angstroms from microcrystals grown in lipidic cubic phases. Science 277(5332):1676–1681CrossRefGoogle Scholar
  28. 28.
    Li D, Boland C, Walsh K, Caffrey M (2012) Use of a robot for high-throughput crystallization of membrane proteins in lipidic mesophases. J Vis Exp 67:e4000Google Scholar
  29. 29.
    Cherezov V, Peddi A, Muthusubramaniam L, Zheng YF, Caffrey M (2004) A robotic system for crystallizing membrane and soluble proteins in lipidic mesophases. Acta Crystallogr D 60(Pt 10):1795–1807CrossRefGoogle Scholar
  30. 30.
    Ai X, Caffrey M (2000) Membrane protein crystallization in lipidic mesophases: detergent effects. Biophys J 79(1):394–405CrossRefGoogle Scholar
  31. 31.
    Caffrey M (1987) Kinetics and mechanism of transitions involving the lamellar, cubic, inverted hexagonal, and fluid isotropic phases of hydrated monoacylglycerides monitored by time-resolved X-ray diffraction. Biochemistry 26(20):6349–6363CrossRefGoogle Scholar
  32. 32.
    Cherezov V, Fersi H, Caffrey M (2001) Crystallization screens: compatibility with the lipidic cubic phase for in meso crystallization of membrane proteins. Biophys J 81(1):225–242CrossRefGoogle Scholar
  33. 33.
    Cherezov V, Liu W, Derrick JP, Luan B, Aksimentiev A, Katritch V, Caffrey M (2008) In meso crystal structure and docking simulations suggest an alternative proteoglycan binding site in the OpcA outer membrane adhesin. Proteins 71(1):24–34CrossRefGoogle Scholar
  34. 34.
    Cherezov V, Yamashita E, Liu W, Zhalnina M, Cramer WA, Caffrey M (2006) In meso structure of the cobalamin transporter, BtuB, at 1.95 Å resolution. J Mol Biol 364(4):716–734CrossRefGoogle Scholar
  35. 35.
    Hofer N, Aragao D, Caffrey M (2010) Crystallizing transmembrane peptides in lipidic mesophases. Biophys J 99(3):L23–25CrossRefGoogle Scholar
  36. 36.
    Cherezov V, Clogston J, Papiz MZ, Caffrey M (2006) Room to move: crystallizing membrane proteins in swollen lipidic mesophases. J Mol Biol 357(5):1605–1618CrossRefGoogle Scholar
  37. 37.
    Lyons JA, Aragao D, Slattery O, Pisliakov AV, Soulimane T, Caffrey M (2012) Structural insights into electron transfer in caa3-type cytochrome oxidase. Nature 487(7408):514–518CrossRefGoogle Scholar
  38. 38.
    Li D, Caffrey M (2011) Lipid cubic phase as a membrane mimetic for integral membrane protein enzymes. Proc Natl Acad Sci U S A 108(21):8639–8644CrossRefGoogle Scholar
  39. 39.
    Li D, Lyons JA, Pye VE, Vogeley L, Aragao D, Kenyon CP, Shah ST, Doherty C, Aherne M, Caffrey M (2013) Crystal structure of the integral membrane diacylglycerol kinase. Nature 497(7450):521–524CrossRefGoogle Scholar
  40. 40.
    Li D, Howe N, Dukkipati A, Shah ST, Bax BD, Edge C, Bridges A, Hardwicke P, Singh OM, Giblin G, Pautsch A, Pfau R, Schnapp G, Wang M, Olieric V, Caffrey M (2014) Crystallizing membrane proteins in the lipidic mesophase. experience with human prostaglandin E2 synthase 1 and an evolving strategy. Cryst Growth Des 14(4):2034–2047CrossRefGoogle Scholar
  41. 41.
    Lyons JA, Parker JL, Solcan N, Brinth A, Li D, Shah STA, Caffrey M, Newstead S (2014) Structural basis for polyspecificity in the POT family of proton-coupled oligopeptide transporters. EMBO Rep 15(8):886–893CrossRefGoogle Scholar
  42. 42.
    Li D, Lee J, Caffrey M (2011) Crystallizing membrane proteins in lipidic mesophases. a host lipid screen. Cryst Growth Des 11(2):530–537CrossRefGoogle Scholar
  43. 43.
    Li D, Shah ST, Caffrey M (2013) Host lipid and temperature as important screening variables for crystallizing integral membrane proteins in lipidic mesophases. Trials with diacylglycerol kinase. Cryst Growth Des 13(7):2846–2857CrossRefGoogle Scholar
  44. 44.
    Tan J, Rouse SL, Li D, Pye VE, Vogeley L, Brinth AR, El Arnaout T, Whitney JC, Howell PL, Sansom MSP, Caffrey M (2014) A conformational landscape for alginate secretion across the outer membrane of Pseudomonas aeruginosa. Acta Crystallogr D 70(Pt 8):2054–2068CrossRefGoogle Scholar
  45. 45.
    Rasmussen SGF, DeVree BT, Zou Y, Kruse AC, Chung KY, Kobilka TS, Thian FS, Chae PS, Pardon E, Calinski D, Mathiesen JM, Shah STA, Lyons JA, Caffrey M, Gellman SH, Steyaert J, Skiniotis G, Weis WI, Sunahara RK, Kobilka BK (2011) Crystal structure of the β(2)Adrenergic receptor-Gs protein complex. Nature 477(7366):549–555CrossRefGoogle Scholar
  46. 46.
    Li D, Pye VE, Caffrey M (2015) Experimental phasing for structure determination using membrane-protein crystals grown by the lipid cubic phase method. Acta Crystallogr D 71(Pt 1):104–122CrossRefGoogle Scholar
  47. 47.
    Li D, Boland C, Aragao D, Walsh K, Caffrey M (2012) Harvesting and cryo-cooling crystals of membrane proteins grown in lipidic mesophases for structure determination by macromolecular crystallography. J Vis Exp 67:4001Google Scholar
  48. 48.
    Liu W, Cherezov V (2011) Crystallization of membrane proteins in lipidic mesophases. J Vis Exp 49:2501Google Scholar
  49. 49.
    Huang CY, Olieric V, Ma P, Howe N, Vogeley L, Liu X, Warshamanage R, Weinert T, Panepucci E, Kobilka B, Diederichs K, Wang M, Caffrey M (2016) In meso in situ serial X-ray crystallography of soluble and membrane proteins at cryogenic temperatures. Acta Crystallogr D 72(Pt 1):93–112CrossRefGoogle Scholar
  50. 50.
    Huang C-Y, Olieric V, Ma P, Panepucci E, Diederichs K, Wang M, Caffrey M (2015) In meso in situ serial X-ray crystallography of soluble and membrane proteins. Acta Crystallogr D 71(Pt 6):1238–1256CrossRefGoogle Scholar
  51. 51.
    Weierstall U, James D, Wang C, White TA, Wang D, Liu W, Spence JCH, Doak RB, Nelson G, Fromme P, Fromme R, Grotjohann I, Kupitz C, Zatsepin NA, Liu H, Basu S, Wacker D, Han GW, Katritch V, Boutet S, Messerschmidt M, Williams GJ, Koglin JE, Seibert MM, Klinker M, Gati C, Shoeman RL, Barty A, Chapman HN, Kirian RA, Beyerlein KR, Stevens RC, Li D, Shah STA, Howe N, Caffrey M, Cherezov V (2014) Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography. Nat Commun 5:3309CrossRefGoogle Scholar
  52. 52.
    Clogston J, Rathman J, Tomasko D, Walker H, Caffrey M (2000) Phase behavior of a monoacylglycerol: (Myverol 18–99 K)/water system. Chem Phys Lipids 107(2):191–220CrossRefGoogle Scholar
  53. 53.
    Caffrey M, Porter C (2010) Crystallizing membrane proteins for structure determination using lipidic mesophases. J Vis Exp 45:e1712Google Scholar
  54. 54.
    Salvati Manni L, Zabara A, Osornio YM, Schoppe J, Batyuk A, Pluckthun A, Siegel JS, Mezzenga R, Landau EM (2015) Phase behavior of a designed cyclopropyl analogue of monoolein: implications for low-temperature membrane protein crystallization. Angew Chem Int Ed Engl 54(3):1027–1031CrossRefGoogle Scholar
  55. 55.
    Barauskas J, Landh T (2003) Phase behavior of the phytantriol/water system. Langmuir 19(23):9562–9565CrossRefGoogle Scholar
  56. 56.
    Borshchevskiy V, Molseeva E, Kuklin A, Buldt G, Hato M, Gordeliy V (2010) Isoprenoid-chained lipid beta-XylOC(16 + 4)—a novel molecule for in meso membrane protein crystallization. J Cryst Growth 312(22):3326–3330CrossRefGoogle Scholar
  57. 57.
    Ishchenko A, Peng L, Zinovev E, Vlasov A, Lee SC, Kuklin A, Mishin A, Borshchevskiy V, Zhang Q, Cherezov V (2017) Chemically stable lipids for membrane protein crystallization. Cryst Growth Des 17(6):3502–3511CrossRefGoogle Scholar
  58. 58.
    Broecker J, Keller S (2013) Impact of urea on detergent micelle properties. Langmuir 29(27):8502–8510CrossRefGoogle Scholar
  59. 59.
    Li D, Caffrey M (2014) Renaturing membrane proteins in the lipid cubic phase, a nanoporous membrane mimetic. Sci Rep 4:5806CrossRefGoogle Scholar
  60. 60.
    Clogston J, Craciun G, Hart DJ, Caffrey M (2005) Controlling release from the lipidic cubic phase by selective alkylation. J Control Release 102(2):441–461CrossRefGoogle Scholar
  61. 61.
    Misquitta Y, Caffrey M (2003) Detergents destabilize the cubic phase of monoolein: implications for membrane protein crystallization. Biophys J 85(5):3084–3096CrossRefGoogle Scholar
  62. 62.
    Chae PS, Rasmussen SGF, Rana RR, Gotfryd K, Chandra R, Goren MA, Kruse AC, Nurva S, Loland CJ, Pierre Y, Drew D, Popot J-L, Picot D, Fox BG, Guan L, Gether U, Byrne B, Kobilka B, Gellman SH (2010) Maltose-neopentyl glycol (MNG) amphiphiles for solubilization, stabilization and crystallization of membrane proteins. Nat Methods 7(12):1003–1008CrossRefGoogle Scholar
  63. 63.
    Champeil P, Orlowski S, Babin S, Lund S, le Maire M, Moller J, Lenoir G, Montigny C (2016) A robust method to screen detergents for membrane protein stabilization, revisited. Anal Biochem 511:31–35CrossRefGoogle Scholar
  64. 64.
    Caffrey M (2015) A comprehensive review of the lipid cubic phase or in meso method for crystallizing membrane and soluble proteins and complexes. Acta Crystallogr F 71(Pt 1):3–18CrossRefGoogle Scholar
  65. 65.
    Caffrey M, Cherezov V (2009) Crystallizing membrane proteins using lipidic mesophases. Nat Protoc 4(5):706–731CrossRefGoogle Scholar
  66. 66.
    Ridell A, Ekelund K, Evertsson H, Engström S (2003) On the water content of the solvent/monoolein/water sponge (L3) phase. Colloids Surf A Physicochem Eng Asp 228(1):17–24CrossRefGoogle Scholar
  67. 67.
    Engström S, Alfons K, Rasmusson M, Ljusberg-Wahren H (1998) Solvent-induced sponge (L3) phases in the solvent-monoolein-water system. In: Lindman B, Ninham BW (eds) The colloid science of lipids: new paradigms for self-assembly in science and technology. Steinkopff, Darmstadt, pp 93–98. doi: 10.1007/BFb0117965
  68. 68.
    Wadsten P, Wohri AB, Snijder A, Katona G, Gardiner AT, Cogdell RJ, Neutze R, Engstrom S (2006) Lipidic sponge phase crystallization of membrane proteins. J Mol Biol 364(1):44–53CrossRefGoogle Scholar
  69. 69.
    Wöhri AB, Johansson LC, Wadsten-Hindrichsen P, Wahlgren WY, Fischer G, Horsefield R, Katona G, Nyblom M, Öberg F, Young G, Cogdell RJ, Fraser NJ, Engström S, Neutze R (2008) A lipidic-sponge phase screen for membrane protein crystallization. Structure 16(7):1003–1009CrossRefGoogle Scholar
  70. 70.
    Cherezov V, Liu J, Griffith M, Hanson MA, Stevens RC (2008) LCP-FRAP assay for pre-screening membrane proteins for in meso crystallization. Cryst Growth Des 8(12):4307–4315CrossRefGoogle Scholar
  71. 71.
    Kenworthy AK, Simon SA, McIntosh TJ (1995) Structure and phase behavior of lipid suspensions containing phospholipids with covalently attached poly (ethylene glycol). Biophys J 68(5):1903–1920CrossRefGoogle Scholar
  72. 72.
    Imberg A, Evertsson H, Stilbs P, Kriechbaum M, Engström S (2003) On the self-assembly of monoolein in mixtures of water and a polar aprotic solvent. J Phys Chem B 107(10):2311–2318CrossRefGoogle Scholar
  73. 73.
    Takahashi H, Matsuo A, Hatta I (2000) Effects of chaotropic and kosmotropic solutes on the structure of lipid cubic phase: monoolein-water systems. Mol Cryst Liq Cryst Sci Technol Sect A Mol Cryst Liq Cryst 347(1):231–238CrossRefGoogle Scholar
  74. 74.
    Evertsson H, Stilbs P, Lindblom G, Engström S (2002) NMR self diffusion measurements of the Monooleoylglycerol/Poly ethylene glycol/water L3 phase. Colloids Surf B Biointerfaces 26(1):21–29CrossRefGoogle Scholar
  75. 75.
    Liu W, Caffrey M (2005) Gramicidin structure and disposition in highly curved membranes. J Struct Biol 150(1):23–40CrossRefGoogle Scholar
  76. 76.
    Cherezov V, Caffrey M (2007) Membrane protein crystallization in lipidic mesophases. A mechanism study using X-ray microdiffraction. Faraday discussions 136:195–212Google Scholar
  77. 77.
    Qutub Y, Reviakine I, Maxwell C, Navarro J, Landau EM, Vekilov PG (2004) Crystallization of transmembrane proteins in cubo: mechanisms of crystal growth and defect formation. J Mol Biol 343(5):1243–1254CrossRefGoogle Scholar
  78. 78.
    Caffrey M (2008) On the mechanism of membrane protein crystallization in lipidic mesophases. Cryst Growth Des 8(12):4244–4254CrossRefGoogle Scholar
  79. 79.
    Aherne M, Lyons JA, Caffrey M (2012) A fast, simple and robust protocol for growing crystals in the lipidic cubic phase. J Appl Crystallogr 45(Pt 6):1330–1333CrossRefGoogle Scholar
  80. 80.
    Kobilka B (2013) The structural basis of G-protein-coupled receptor signaling (Nobel Lecture). Angew Chem Int Ed Engl 52(25):6380–6388CrossRefGoogle Scholar
  81. 81.
    Santos R, Ursu O, Gaulton A, Bento AP, Donadi RS, Bologa CG, Karlsson A, Al-Lazikani B, Hersey A, Oprea TI, Overington JP (2017) A comprehensive map of molecular drug targets. Nat Rev Drug Discov 16(1):19–34CrossRefGoogle Scholar
  82. 82.
    Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SGF, Thian FS, Kobilka TS, Choi H-J, Kuhn P, Weis WI, Kobilka BK, Stevens RC (2007) High resolution crystal structure of an engineered human β(2)-Adrenergic G protein-coupled receptor. Science 318(5854):1258–1265CrossRefGoogle Scholar
  83. 83.
    Rosenbaum DM, Cherezov V, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Yao XJ, Weis WI, Stevens RC, Kobilka BK (2007) GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function. Science 318(5854):1266–1273CrossRefGoogle Scholar
  84. 84.
    Rasmussen SG, DeVree BT, Zou Y, Kruse AC, Chung KY, Kobilka TS, Thian FS, Chae PS, Pardon E, Calinski D, Mathiesen JM, Shah ST, Lyons JA, Caffrey M, Gellman SH, Steyaert J, Skiniotis G, Weis WI, Sunahara RK, Kobilka BK (2011) Crystal structure of the beta2 adrenergic receptor-Gs protein complex. Nature 477(7366):549–555CrossRefGoogle Scholar
  85. 85.
    Kang Y, Zhou XE, Gao X, He Y, Liu W, Ishchenko A, Barty A, White TA, Yefanov O, Han GW, Xu Q, de Waal PW, Ke J, Tan MH, Zhang C, Moeller A, West GM, Pascal BD, Van Eps N, Caro LN, Vishnivetskiy SA, Lee RJ, Suino-Powell KM, Gu X, Pal K, Ma J, Zhi X, Boutet S, Williams GJ, Messerschmidt M, Gati C, Zatsepin NA, Wang D, James D, Basu S, Roy-Chowdhury S, Conrad CE, Coe J, Liu H, Lisova S, Kupitz C, Grotjohann I, Fromme R, Jiang Y, Tan M, Yang H, Li J, Wang M, Zheng Z, Li D, Howe N, Zhao Y, Standfuss J, Diederichs K, Dong Y, Potter CS, Carragher B, Caffrey M, Jiang H, Chapman HN, Spence JC, Fromme P, Weierstall U, Ernst OP, Katritch V, Gurevich VV, Griffin PR, Hubbell WL, Stevens RC, Cherezov V, Melcher K, Xu HE (2015) Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature 523(7562):561–567CrossRefGoogle Scholar
  86. 86.
    Serrano-Vega MJ, Magnani F, Shibata Y, Tate CG (2008) Conformational thermostabilization of the β1-adrenergic receptor in a detergent-resistant form. Proc Natl Acad Sci U S A 105(3):877–882CrossRefGoogle Scholar
  87. 87.
    Warne T, Serrano-Vega MJ, Baker JG, Moukhametzianov R, Edwards PC, Henderson R, Leslie AGW, Tate CG, Schertler GFX (2008) Structure of a [bgr]1-adrenergic G-protein-coupled receptor. Nature 454(7203):486–491CrossRefGoogle Scholar
  88. 88.
    Lebon G, Warne T, Tate CG (2012) Agonist-bound structures of G protein-coupled receptors. Curr Opin Struct Biol 22(4):482–490CrossRefGoogle Scholar
  89. 89.
    Lebon G, Warne T, Edwards PC, Bennett K, Langmead CJ, Leslie AG, Tate CG (2011) Agonist-bound adenosine A2A receptor structures reveal common features of GPCR activation. Nature 474(7352):521–525CrossRefGoogle Scholar
  90. 90.
    Sun B, Bachhawat P, Chu ML-H, Wood M, Ceska T, Sands ZA, Mercier J, Lebon F, Kobilka TS, Kobilka BK (2017) Crystal structure of the adenosine A2A receptor bound to an antagonist reveals a potential allosteric pocket. Proc Natl Acad Sci U S A 114(8):2066–2071CrossRefGoogle Scholar
  91. 91.
    Lanyi JK (2004) Bacteriorhodopsin. Annu Rev Physiol 66(1):665–688CrossRefGoogle Scholar
  92. 92.
    Nogly P, Panneels V, Nelson G, Gati C, Kimura T, Milne C, Milathianaki D, Kubo M, Wu W, Conrad C, Coe J, Bean R, Zhao Y, Bath P, Dods R, Harimoorthy R, Beyerlein KR, Rheinberger J, James D, DePonte D, Li C, Sala L, Williams GJ, Hunter MS, Koglin JE, Berntsen P, Nango E, Iwata S, Chapman HN, Fromme P, Frank M, Abela R, Boutet S, Barty A, White TA, Weierstall U, Spence J, Neutze R, Schertler G, Standfuss J (2016) Lipidic cubic phase injector is a viable crystal delivery system for time-resolved serial crystallography. Nat Commun 7:12314CrossRefGoogle Scholar
  93. 93.
    Misquitta LV, Misquitta Y, Cherezov V, Slattery O, Mohan JM, Hart D, Zhalnina M, Cramer WA, Caffrey M (2004) Membrane protein crystallization in lipidic mesophases with tailored bilayers. Structure 12(12):2113–2124CrossRefGoogle Scholar
  94. 94.
    Kato HE, Zhang F, Yizhar O, Ramakrishnan C, Nishizawa T, Hirata K, Ito J, Aita Y, Tsukazaki T, Hayashi S, Hegemann P, Maturana AD, Ishitani R, Deisseroth K, Nureki O (2012) Crystal structure of the channelrhodopsin light-gated cation channel. Nature 482(7385):369–374CrossRefGoogle Scholar
  95. 95.
    Gordeliy VI, Labahn J, Moukhametzianov R, Efremov R, Granzin J, Schlesinger R, Buldt G, Savopol T, Scheidig AJ, Klare JP, Engelhard M (2002) Molecular basis of transmembrane signalling by sensory rhodopsin II-transducer complex. Nature 419(6906):484–487CrossRefGoogle Scholar
  96. 96.
    Zhou X, Levin EJ, Pan Y, McCoy JG, Sharma R, Kloss B, Bruni R, Quick M, Zhou M (2014) Structural basis of the alternating-access mechanism in a bile acid transporter. Nature 505(7484):569–573CrossRefGoogle Scholar
  97. 97.
    Deng D, Sun P, Yan C, Ke M, Jiang X, Xiong L, Ren W, Hirata K, Yamamoto M, Fan S, Yan N (2015) Molecular basis of ligand recognition and transport by glucose transporters. Nature 526(7573):391–396CrossRefGoogle Scholar
  98. 98.
    Taniguchi R, Kato HE, Font J, Deshpande CN, Wada M, Ito K, Ishitani R, Jormakka M, Nureki O (2015) Outward- and inward-facing structures of a putative bacterial transition-metal transporter with homology to ferroportin. Nat Commun 6:8545CrossRefGoogle Scholar
  99. 99.
    Tanaka Y, Hipolito CJ, Maturana AD, Ito K, Kuroda T, Higuchi T, Katoh T, Kato HE, Hattori M, Kumazaki K, Tsukazaki T, Ishitani R, Suga H, Nureki O (2013) Structural basis for the drug extrusion mechanism by a MATE multidrug transporter. Nature 496(7444):247–251CrossRefGoogle Scholar
  100. 100.
    Kusakizako T, Tanaka Y, Hipolito CJ, Kuroda T, Ishitani R, Suga H, Nureki O (2016) LCP crystallization and X-ray diffraction analysis of VcmN, a MATE transporter from Vibrio cholerae. Acta Crystallogr F 72(Pt 7):552–557CrossRefGoogle Scholar
  101. 101.
    Kuk ACY, Mashalidis EH, Lee S-Y (2017) Crystal structure of the MOP flippase MurJ in an inward-facing conformation. Nat Struct Mol Biol 24(2):171–176CrossRefGoogle Scholar
  102. 102.
    Fukuda M, Takeda H, Kato HE, Doki S, Ito K, Maturana AD, Ishitani R, Nureki O (2015) Structural basis for dynamic mechanism of nitrate/nitrite antiport by NarK. Nat Commun 6:7097CrossRefGoogle Scholar
  103. 103.
    Solcan N, Kwok J, Fowler PW, Cameron AD, Drew D, Iwata S, Newstead S (2012) Alternating access mechanism in the POT family of oligopeptide transporters. EMBO J 31(16):3411–3421CrossRefGoogle Scholar
  104. 104.
    Quistgaard EM, Low C, Guettou F, Nordlund P (2016) Understanding transport by the major facilitator superfamily (MFS): structures pave the way. Nat Rev Mol Cell Biol 17(2):123–132CrossRefGoogle Scholar
  105. 105.
    Kaback HR, Smirnova I, Kasho V, Nie Y, Zhou Y (2011) The Alternating access transport mechanism in LacY. J Membr Biol 239(1–2):85–93CrossRefGoogle Scholar
  106. 106.
    Bao Z, Qi X, Hong S, Xu K, He F, Zhang M, Chen J, Chao D, Zhao W, Li D, Wang J, Zhang P (2017) Structure and mechanism of a group-I cobalt energy coupling factor transporter. Cell Res 27(5):675–687CrossRefGoogle Scholar
  107. 107.
    Moitra K (2015) Overcoming multidrug resistance in cancer stem cells. Biomed Res Int 2015:635745CrossRefGoogle Scholar
  108. 108.
    Wang J, Yan C, Li Y, Hirata K, Yamamoto M, Yan N, Hu Q (2014) Crystal structure of a bacterial homologue of SWEET transporters. Cell Res 24(12):1486–1489CrossRefGoogle Scholar
  109. 109.
    Lee Y, Nishizawa T, Yamashita K, Ishitani R, Nureki O (2015) Structural basis for the facilitative diffusion mechanism by SemiSWEET transporter. Nat Commun 6:6112CrossRefGoogle Scholar
  110. 110.
    Xu Y, Tao Y, Cheung LS, Fan C, Chen LQ, Xu S, Perry K, Frommer WB, Feng L (2014) Structures of bacterial homologues of SWEET transporters in two distinct conformations. Nature 515(7527):448–452CrossRefGoogle Scholar
  111. 111.
    Feng L, Frommer WB (2015) Structure and function of SemiSWEET and SWEET sugar transporters. Trends Biochem Sci 40(8):480–486Google Scholar
  112. 112.
    Santos JS, Asmar-Rovira GA, Han GW, Liu W, Syeda R, Cherezov V, Baker KA, Stevens RC, Montal M (2012) Crystal structure of a voltage-gated K+ channel pore module in a closed state in lipid membranes. J Biol Chem 287(51):43063–43070CrossRefGoogle Scholar
  113. 113.
    Takeda H, Hattori M, Nishizawa T, Yamashita K, Shah ST, Caffrey M, Maturana AD, Ishitani R, Nureki O (2014) Structural basis for ion selectivity revealed by high-resolution crystal structure of Mg2+ channel MgtE. Nat Commun 5:5374CrossRefGoogle Scholar
  114. 114.
    Liao J, Marinelli F, Lee C, Huang Y, Faraldo-Gómez JD, Jiang Y (2016) Mechanism of extracellular ion exchange and binding-site occlusion in the sodium-calcium exchanger. Nat Struct Mol Biol 23(6):590–599CrossRefGoogle Scholar
  115. 115.
    Liao J, Li H, Zeng W, Sauer DB, Belmares R, Jiang Y (2012) Structural insight into the ion-exchange mechanism of the sodium/calcium exchanger. Science 335(6069):686–690CrossRefGoogle Scholar
  116. 116.
    Waight AB, Pedersen BP, Schlessinger A, Bonomi M, Chau BH, Roe-Zurz Z, Risenmay AJ, Sali A, Stroud RM (2013) Structural basis for alternating access of a eukaryotic calcium/proton exchanger. Nature 499(7456):107–110CrossRefGoogle Scholar
  117. 117.
    Su M, Gao F, Yuan Q, Mao Y, Li DL, Guo Y, Yang C, Wang XH, Bruni R, Kloss B, Zhao H, Zeng Y, Zhang FB, Marks AR, Hendrickson WA, Chen YH (2017) Structural basis for conductance through TRIC cation channels. Nat Commun 8:15103CrossRefGoogle Scholar
  118. 118.
    Kasuya G, Hiraizumi M, Maturana AD, Kumazaki K, Fujiwara Y, Liu K, Nakada-Nakura Y, Iwata S, Tsukada K, Komori T, Uemura S, Goto Y, Nakane T, Takemoto M, Kato HE, Yamashita K, Wada M, Ito K, Ishitani R, Hattori M, Nureki O (2016) Crystal structures of the TRIC trimeric intracellular cation channel orthologues. Cell Res 26(12):1288–1301CrossRefGoogle Scholar
  119. 119.
    Yang H, Hu M, Guo J, Ou X, Cai T, Liu Z (2016) Pore architecture of TRIC channels and insights into their gating mechanism. Nature 538(7626):537–541CrossRefGoogle Scholar
  120. 120.
    Shi Y, Burn P (2004) Lipid metabolic enzymes: emerging drug targets for the treatment of obesity. Nat Rev Drug Discov 3(8):695–710CrossRefGoogle Scholar
  121. 121.
    Vogeley L, El Arnaout T, Bailey J, Stansfeld PJ, Boland C, Caffrey M (2016) Structural basis of lipoprotein signal peptidase II action and inhibition by the antibiotic globomycin. Science 351(6275):876–880CrossRefGoogle Scholar
  122. 122.
    Sciara G, Clarke OB, Tomasek D, Kloss B, Tabuso S, Byfield R, Cohn R, Banerjee S, Rajashankar KR, Slavkovic V, Graziano JH, Shapiro L, Mancia F (2014) Structural basis for catalysis in a CDP-alcohol phosphotransferase. Nat Commun 5:4068CrossRefGoogle Scholar
  123. 123.
    Clarke OB, Tomasek D, Jorge CD, Dufrisne MB, Kim M, Banerjee S, Rajashankar KR, Shapiro L, Hendrickson WA, Santos H, Mancia F (2015) Structural basis for phosphatidylinositol-phosphate biosynthesis. Nat Commun 0:8505CrossRefGoogle Scholar
  124. 124.
    Bai Y, McCoy JG, Levin EJ, Sobrado P, Rajashankar KR, Fox BG, Zhou M (2015) X-ray structure of a mammalian stearoyl-CoA desaturase. Nature 524(7564):252–256CrossRefGoogle Scholar
  125. 125.
    Lorch M, Faham S, Kaiser C, Weber I, Mason AJ, Bowie JU, Glaubitz C (2005) How to prepare membrane proteins for solid-state NMR: a case study on the alpha-helical integral membrane protein diacylglycerol kinase from E. coli. Chembiochem A Eur J Chem Biol 6(9):1693–1700Google Scholar
  126. 126.
    Lau FW, Chen X, Bowie JU (1999) Active sites of diacylglycerol kinase from Escherichia coli are shared between subunits. Biochemistry 38(17):5521–5527CrossRefGoogle Scholar
  127. 127.
    Li D, Stansfeld PJ, Sansom MS, Keogh A, Vogeley L, Howe N, Lyons JA, Aragao D, Fromme P, Fromme R, Basu S, Grotjohann I, Kupitz C, Rendek K, Weierstall U, Zatsepin NA, Cherezov V, Liu W, Bandaru S, English NJ, Gati C, Barty A, Yefanov O, Chapman HN, Diederichs K, Messerschmidt M, Boutet S, Williams GJ, Marvin Seibert M, Caffrey M (2015) Ternary structure reveals mechanism of a membrane diacylglycerol kinase. Nat Commun 6:10140CrossRefGoogle Scholar
  128. 128.
    Badola P, Sanders CR 2nd (1997) Escherichia coli diacylglycerol kinase is an evolutionarily optimized membrane enzyme and catalyzes direct phosphoryl transfer. J Biol Chem 272(39):24176–24182CrossRefGoogle Scholar
  129. 129.
    Koeberle A, Werz O (2015) Perspective of microsomal prostaglandin E2 synthase-1 as drug target in inflammation-related disorders. Biochem Pharmacol 98(1):1–15CrossRefGoogle Scholar
  130. 130.
    Weinert T, Olieric V, Waltersperger S, Panepucci E, Chen L, Zhang H, Zhou D, Rose J, Ebihara A, Kuramitsu S, Li D, Howe N, Schnapp G, Pautsch A, Bargsten K, Prota AE, Surana P, Kottur J, Nair DT, Basilico F, Cecatiello V, Pasqualato S, Boland A, Weichenrieder O, Wang B-C, Steinmetz MO, Caffrey M, Wang M (2015) Fast native-SAD phasing for routine macromolecular structure determination. Nat Methods 12(2):131–133CrossRefGoogle Scholar
  131. 131.
    Dobrzyn A, Ntambi JM (2005) Stearoyl-CoA desaturase as a new drug target for obesity treatment. Obes Rev Off J Int Assoc Study Obes 6(2):169–174CrossRefGoogle Scholar
  132. 132.
    Katona G, Andreasson U, Landau EM, Andreasson LE, Neutze R (2003) Lipidic cubic phase crystal structure of the photosynthetic reaction centre from Rhodobacter sphaeroides at 2.35 Å resolution. J Mol Biol 331(3):681–692CrossRefGoogle Scholar
  133. 133.
    Charrin S, Jouannet S, Boucheix C, Rubinstein E (2014) Tetraspanins at a glance. J Cell Sci 127(Pt 17):3641–3648CrossRefGoogle Scholar
  134. 134.
    Suzuki H, Nishizawa T, Tani K, Yamazaki Y, Tamura A, Ishitani R, Dohmae N, Tsukita S, Nureki O, Fujiyoshi Y (2014) Crystal structure of a claudin provides insight into the architecture of tight junctions. Science 344(6181):304–307CrossRefGoogle Scholar
  135. 135.
    Zimmerman B, Kelly B, McMillan BJ, Seegar TC, Dror RO, Kruse AC, Blacklow SC (2016) Crystal structure of a full-length human tetraspanin reveals a cholesterol-binding pocket. Cell 167(4):1041–1051 e1011Google Scholar
  136. 136.
    Joh NH, Wang T, Bhate MP, Acharya R, Wu Y, Grabe M, Hong M, Grigoryan G, DeGrado WF (2014) De novo design of a transmembrane Zn(2+)-transporting four-helix bundle. Science 346(6216):1520–1524CrossRefGoogle Scholar
  137. 137.
    Trenker R, Call ME, Call MJ (2015) Crystal structure of the glycophorin a transmembrane dimer in lipidic cubic phase. J Am Chem Soc 137(50):15676–15679CrossRefGoogle Scholar
  138. 138.
    Thomaston JL, Alfonso-Prieto M, Woldeyes RA, Fraser JS, Klein ML, Fiorin G, DeGrado WF (2015) High-resolution structures of the M2 channel from influenza A virus reveal dynamic pathways for proton stabilization and transduction. Proc Natl Acad Sci U S A 112(46):14260–14265CrossRefGoogle Scholar
  139. 139.
    Takeda K, Kaisho T, Akira S (2003) Toll-like receptors. Annu Rev Immunol 21:335–376CrossRefGoogle Scholar
  140. 140.
    Barclay AN (2003) Membrane proteins with immunoglobulin-like domains—a master superfamily of interaction molecules. Semin Immunol 15(4):215–223CrossRefGoogle Scholar
  141. 141.
    Waters JP, Pober JS, Bradley JR (2013) Tumour necrosis factor and cancer. J Pathol 230(3):241–248CrossRefGoogle Scholar
  142. 142.
    Hirayasu K, Arase H (2015) Functional and genetic diversity of leukocyte immunoglobulin-like receptor and implication for disease associations. J Hum Genet 60(11):703–708CrossRefGoogle Scholar
  143. 143.
    Dolan J, Walshe K, Alsbury S, Hokamp K, O’Keeffe S, Okafuji T, Miller SF, Tear G, Mitchell KJ (2007) The extracellular Leucine-Rich repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns. BMC Genom 8(1):320CrossRefGoogle Scholar
  144. 144.
    Klug L, Daum G (2014) Yeast lipid metabolism at a glance. FEMS Yeast Res 14(3):369–388CrossRefGoogle Scholar
  145. 145.
    Zanger UM, Schwab M (2013) Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther 138(1):103–141CrossRefGoogle Scholar
  146. 146.
    Lomize AL, Lomize MA, Krolicki SR, Pogozheva ID (2017) Membranome: a database for proteome-wide analysis of single-pass membrane proteins. Nucleic Acids Res 45 (Database issue):D250–D255Google Scholar
  147. 147.
    Schmidt HR, Zheng S, Gurpinar E, Koehl A, Manglik A, Kruse AC (2016) Crystal structure of the human sigma1 receptor. Nature 532(7600):527–530CrossRefGoogle Scholar
  148. 148.
    Bourret RB, Silversmith RE (2010) Two-component signal transduction. Curr Opin Microbiol 13(2):113–115CrossRefGoogle Scholar
  149. 149.
    Bhate Manasi P, Molnar Kathleen S, Goulian M, DeGrado William F (2015) Signal transduction in histidine kinases: insights from new structures. Structure 23(6):981–994CrossRefGoogle Scholar
  150. 150.
    Gushchin I, Melnikov I, Polovinkin V, Ishchenko A, Yuzhakova A, Buslaev P, Bourenkov G, Grudinin S, Round E, Balandin T, Borshchevskiy V, Willbold D, Leonard G, Buldt G, Popov A, Gordeliy V (2017) Mechanism of transmembrane signaling by sensor histidine kinases. Science 356(6342):1043–1049Google Scholar
  151. 151.
    Kumazaki K, Kishimoto T, Furukawa A, Mori H, Tanaka Y, Dohmae N, Ishitani R, Tsukazaki T, Nureki O (2014) Crystal structure of Escherichia coli YidC, a membrane protein chaperone and insertase. Sci Rep 4:7299CrossRefGoogle Scholar
  152. 152.
    Kumazaki K, Chiba S, Takemoto M, Furukawa A, K-i Nishiyama, Sugano Y, Mori T, Dohmae N, Hirata K, Nakada-Nakura Y, Maturana AD, Tanaka Y, Mori H, Sugita Y, Arisaka F, Ito K, Ishitani R, Tsukazaki T, Nureki O (2014) Structural basis of Sec-independent membrane protein insertion by YidC. Nature 509(7501):516–520CrossRefGoogle Scholar
  153. 153.
    Tanaka Y, Sugano Y, Takemoto M, Mori T, Furukawa A, Kusakizako T, Kumazaki K, Kashima A, Ishitani R, Sugita Y, Nureki O, Tsukazaki T (2015) Crystal structures of SecYEG in lipidic cubic phase elucidate a precise resting and a peptide-bound state. Cell Rep 13(8):1561–1568CrossRefGoogle Scholar
  154. 154.
    Efremov RG, Sazanov LA (2012) Structure of Escherichia coli OmpF porin from lipidic mesophase. J Struct Biol 178(3):311–318CrossRefGoogle Scholar
  155. 155.
    Fairman JW, Dautin N, Wojtowicz D, Liu W, Noinaj N, Barnard TJ, Udho E, Przytycka TM, Cherezov V, Buchanan SK (2012) Crystal structures of the outer membrane domain of intimin and invasin from enterohemorrhagic E. coli and enteropathogenic Y. pseudotuberculosis. Structure 20(7):1233–1243CrossRefGoogle Scholar
  156. 156.
    Cheng A, Hummel B, Qiu H, Caffrey M (1998) A simple mechanical mixer for small viscous lipid-containing samples. Chem Phys Lipids 95(1):11–21CrossRefGoogle Scholar
  157. 157.
    McPherson A, Gavira JA (2014) Introduction to protein crystallization. Acta Crystallogr F 70(Pt 1):2–20CrossRefGoogle Scholar
  158. 158.
    Cherezov V, Caffrey M (2003) Nano-volume plates with excellent optical properties for fast, inexpensive crystallization screening of membrane proteins. J Appl Crystallogr 36(6):1372–1377CrossRefGoogle Scholar
  159. 159.
    Cherezov V, Caffrey M (2006) Picolitre-scale crystallization of membrane proteins. J Appl Crystallogr 39(4):604–606CrossRefGoogle Scholar
  160. 160.
    Kissick DJ, Wanapun D, Simpson GJ (2011) Second-order nonlinear optical imaging of chiral crystals. Annu Rev Anal Chem 4:419–437CrossRefGoogle Scholar
  161. 161.
    Liu W, Hanson MA, Stevens RC, Cherezov V (2010) LCP-Tm: an assay to measure and understand stability of membrane proteins in a membrane environment. Biophys J 98(8):1539–1548CrossRefGoogle Scholar
  162. 162.
    Cherezov V, Abola E, Stevens RC (2010) Toward drug design: recent progress in the structure determination of GPCRs, a membrane protein family with high potential as pharmaceutical targets. Methods Mol Biol 654:141–168CrossRefGoogle Scholar
  163. 163.
    Olieric V, Weinert T, Finke AD, Anders C, Li D, Olieric N, Borca CN, Steinmetz MO, Caffrey M, Jinek M, Wang M (2016) Data-collection strategy for challenging native SAD phasing. Acta Crystallogr D 72(3):421–429CrossRefGoogle Scholar
  164. 164.
    Cherezov V, Hanson MA, Griffith MT, Hilgart MC, Sanishvili R, Nagarajan V, Stepanov S, Fischetti RF, Kuhn P, Stevens RC (2009) Rastering strategy for screening and centring of microcrystal samples of human membrane proteins with a sub-10 µm size X-ray synchrotron beam. J R Soc Interface 6(Suppl 5):S587–S597CrossRefGoogle Scholar
  165. 165.
    Chapman HN, Caleman C, Timneanu N (2014) Diffraction before destruction. Philos Trans R Soc B 369(1647):20130313CrossRefGoogle Scholar
  166. 166.
    Caffrey M, Li D, Howe N, Shah STA (2014) ‘Hit and run’ serial femtosecond crystallography of a membrane kinase in the lipid cubic phase. Philos Trans R Soc B 369(1647):20130621CrossRefGoogle Scholar
  167. 167.
    Weierstall U, Spence JC, Doak RB (2012) Injector for scattering measurements on fully solvated biospecies. Rev Sci Instrum 83(3):035108CrossRefGoogle Scholar
  168. 168.
    Weierstall U (2014) Liquid sample delivery techniques for serial femtosecond crystallography. Philos Trans R Soc B 369(1647):20130337CrossRefGoogle Scholar
  169. 169.
    Chapman HN, Fromme P, Barty A, White TA, Kirian RA, Aquila A, Hunter MS, Schulz J, DePonte DP, Weierstall U, Doak RB, Maia FRNC, Martin AV, Schlichting I, Lomb L, Coppola N, Shoeman RL, Epp SW, Hartmann R, Rolles D, Rudenko A, Foucar L, Kimmel N, Weidenspointner G, Holl P, Liang M, Barthelmess M, Caleman C, Boutet S, Bogan MJ, Krzywinski J, Bostedt C, Bajt S, Gumprecht L, Rudek B, Erk B, Schmidt C, Homke A, Reich C, Pietschner D, Struder L, Hauser G, Gorke H, Ullrich J, Herrmann S, Schaller G, Schopper F, Soltau H, Kuhnel K-U, Messerschmidt M, Bozek JD, Hau-Riege SP, Frank M, Hampton CY, Sierra RG, Starodub D, Williams GJ, Hajdu J, Timneanu N, Seibert MM, Andreasson J, Rocker A, Jonsson O, Svenda M, Stern S, Nass K, Andritschke R, Schroter C-D, Krasniqi F, Bott M, Schmidt KE, Wang X, Grotjohann I, Holton JM, Barends TRM, Neutze R, Marchesini S, Fromme R, Schorb S, Rupp D, Adolph M, Gorkhover T, Andersson I, Hirsemann H, Potdevin G, Graafsma H, Nilsson B, Spence JCH (2011) Femtosecond X-ray protein nanocrystallography. Nature 470(7332):73–77CrossRefGoogle Scholar
  170. 170.
    Liu W, Ishchenko A, Cherezov V (2014) Preparation of microcrystals in lipidic cubic phase for serial femtosecond crystallography. Nat Protoc 9(9):2123–2134CrossRefGoogle Scholar
  171. 171.
    Liu W, Wacker D, Gati C, Han GW, James D, Wang D, Nelson G, Weierstall U, Katritch V, Barty A, Zatsepin NA, Li D, Messerschmidt M, Boutet S, Williams GJ, Koglin JE, Seibert MM, Wang C, Shah STA, Basu S, Fromme R, Kupitz C, Rendek KN, Grotjohann I, Fromme P, Kirian RA, Beyerlein KR, White TA, Chapman HN, Caffrey M, Spence JCH, Stevens RC, Cherezov V (2013) Serial femtosecond crystallography of G protein-coupled receptors. Science 342(6165):1521–1524Google Scholar
  172. 172.
    Zhang H, Han GW, Batyuk A, Ishchenko A, White KL, Patel N, Sadybekov A, Zamlynny B, Rudd MT, Hollenstein K, Tolstikova A, White TA, Hunter MS, Weierstall U, Liu W, Babaoglu K, Moore EL, Katz RD, Shipman JM, Garcia-Calvo M, Sharma S, Sheth P, Soisson SM, Stevens RC, Katritch V, Cherezov V (2017) Structural basis for selectivity and diversity in angiotensin II receptors. Nature 544(7650):327–332CrossRefGoogle Scholar
  173. 173.
    Zhang H, Unal H, Gati C, Han GW, Liu W, Zatsepin NA, James D, Wang D, Nelson G, Weierstall U, Sawaya MR, Xu Q, Messerschmidt M, Williams GJ, Boutet S, Yefanov OM, White TA, Wang C, Ishchenko A, Tirupula KC, Desnoyer R, Coe J, Conrad CE, Fromme P, Stevens RC, Katritch V, Karnik SS, Cherezov V (2015) Structure of the angiotensin receptor revealed by serial femtosecond crystallography. Cell 161(4):833–844CrossRefGoogle Scholar
  174. 174.
    Zhang H, Unal H, Desnoyer R, Han GW, Patel N, Katritch V, Karnik SS, Cherezov V, Stevens RC (2015) Structural basis for ligand recognition and functional selectivity at angiotensin receptor. J Biol Chem 290(49):29127–29139CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.National Center for Protein Science Shanghai, Shanghai Science Research Center, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of SciencesShanghaiChina
  2. 2.University of Chinese Academy of SciencesShanghaiChina

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