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Structural Biology Applications of Synchrotron Radiation and X-Ray Free-Electron Lasers

Synchrotron Light Sources and Free-Electron Lasers

Abstract

Third-generation synchrotron radiation (SR) X-rays have transformed structural biology research in the past decades with the advent of high-brilliance undulator X-ray beams. Combined with developments in microfocus beams, area detectors, and data analysis software, it is now possible to determine large complex structures from extremely small (microns in all directions) crystals, as exemplified by the structures of potassium channels, G-protein coupled receptors (GPCRs), ribosomes, and RNA polymerase complexes. The number of depositions in PDB (the Protein Data Bank) is already more than 100,000, the majority of which have been determined by X-rays. Almost all biology, biochemistry, and molecular biology textbooks now contain protein structures to explain their functions in the cell. Now, X-ray free-electron lasers (XFELs) promise to provide new opportunities in structural biology research. They produce X-ray beams with extraordinary properties: 9 to 10 orders of magnitude higher peak brilliance and 1000 times shorter pulse lengths, compared to existing synchrotron radiation beamlines around the world. Diffraction patterns can be recorded from micro and nanocrystals before radiation damage starts to destroy the samples. Using this “diffract-before-destroy” concept, a new area of XFEL biology has arisen, wherein biologically important questions are tackled beyond what is possible using traditional SR. Ultrashort XFEL pulses allow for frozen-in-time fluctuation X-ray scattering with a possibility of expanding isotropic solution scattering. New modes of XFEL pulses such as two-pulse/two-color are being developed for pump-probe femtosecond time-resolved experiments and phasing. Additionally, hybrid methods are increasingly used for challenging biological questions, in which SR and XFEL methods are combined with other methods such as cryo-electron microscopy, NMR, DEER, and optical and atomic force microscopes. Taken together, SR and XFELs provide a portfolio of structural biology tools which continue to enable cutting edge structural biology research of complex molecular machineries.

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References

  • N. Alonso-Garc´ıa, I. Garc´ıa-Rubio, J.A. Manso, R.M. Buey, H. Urien, A. Sonnenberg, G. Jeschke, J.M. de Pereda, Combination of X-ray crystallography, SAXS and DEER to obtain the structure of the FnIII-3,4 domains of integrin α6β4. Acta Crystallogr. D71, 969–985 (2015)

    Google Scholar 

  • J. Amann, W. Berg, V. Blank, F.-J. Decker, Y. Ding, P. Emma, Y. Feng, J. Frisch, D. Fritz, J. Hastings, Z. Huang, J. Krzywinski, R. Lindberg, H. Loos, A. Lutman, H.-D. Nuhn, D. Ratner, J. Rzepiela, D. Shu, Yu. Shvyd’ko, Shvyd’ko, S. Spampinati, S. Stoupin, S. Terentyev, E. Trakhtenberg, D. Walz, J. Welch, J. Wu, A. Zholents, D. Zhu, Demonstration of self-seeding in a hard-X-ray free-electron laser. Nat. Photonics 6, 693–698 (2012)

    Google Scholar 

  • D. Arnlund, L.C. Johansson, C. Wickstrand, A. Barty, G.J. Williams, E. Malmerberg, J. Davidsson, D. Milathianaki, D.P. DePonte, R.L. Shoeman, D. Wang, D. James, G. Katona, S. Westenhoff, T.A. White, A. Aquila, S. Bari, P. Berntsen, M. Bogan, T.B. van Driel, R.B. Doak, K.S. Kjær, M. Frank, R. Fromme, I. Grotjohann, R. Henning, M.S. Hunter, R.A. Kirian, I. Kosheleva, C. Kupitz, M. Liang, A.V. Martin, M.M. Nielsen, M. Messerschmidt, M.M. M. Messerschmidt, M.M. Seibert, J. Sjöhamn, F. Stellato, U. Weierstall, N.A. Zatsepin, J.C. Spence, P. Fromme, I. Schlichting, S. Boutet, G. Groenhof, H.N. Chapman, R. Neutze, Visualizing a protein quake with time-resolved X-ray scattering at a free-electron laser. Nat. Methods 11, 923–926 (2014)

    Google Scholar 

  • K. Ayyer, H.T. Philipp, M.W. Tate, J.L. Wierman, V. Elser, S.M. Gruner, Determination of crystallographic intensities from sparse data. IUCrJ. 2, 29–34 (2015)

    Article  Google Scholar 

  • T.R. Barends, L. Foucar, S. Botha, R.B. Doak, R.L. Shoeman, K. Nass, J.E. Koglin, G.J. Williams, S. Boutet, M. Messerschmidt, I. Schlichting, De novo protein crystal structure determination from X-ray free-electron laser data. Nature 505, 244–247 (2014)

    Article  ADS  Google Scholar 

  • T.R. Barends, L. Foucar, A. Ardevol, K. Nass, A. Aquila, S. Botha, R.B. Doak, K. Falahati, E. Hartmann, M. Hilpert, M. Heinz, M.C. Hoffmann, J. Kofinger, J.E. Koglin, G. Kovacsova, M. Liang, D. Milathianaki, H. Lemke, J. Reinstein, C.M. Roome, R.L. Shoeman, G.J. Williams, I. Burghardt, G. Hummer, S. Boutet, I. Schlichting, Direct observation of ultrafast collective motions in CO myoglobin upon ligand dissociation. Science. Epub ahead of print (2015a)

    Google Scholar 

  • T. Barends, T.A. White, A. Barty, L. Foucar, M. Messerschmidt, R. Alonso-Mori, S. Botha, H. Chapman, R.B. Doak, L. Galli, C. Gati, M. Gutmann, J. Koglin, A. Markvardsen, K. Nass, D. Oberthur, R.L. Shoeman, I. Schlichting, S. Boutet, Effects of self-seeding and crystal post-selection on the quality of Monte Carlo-integrated SFX data. J Synchrotron Radiat. 22, 644–652 (2015b)

    Article  Google Scholar 

  • S. Botha, K. Nass, T.R. Barends, W. Kabsch, B. Latz, F. Dworkowski, L. Foucar, E. Panepucci, M. Wang, R.L. Shoeman, I. Schlichting, R.B. Doak, Room-temperature serial crystallography at synchrotron X-ray sources using slowly flowing free-standing high-viscosity microstreams. Acta Crystallogr. D Biol. Crystallogr. 71, 387–397 (2015)

    Article  Google Scholar 

  • S. Boutet, L. Lomb, G.J. Williams, T.R. Barends, A. Aquila, R.B. Doak, U. Weierstall, D.P. DePonte, J. Steinbrener, R.L. Shoeman, M. Messerschmidt, A. Barty, T.A. White, S. Kassemeyer, R.A. Kirian, M.M. Seibert, P.A. Montanez, C. Kenney, R. Herbst, P. Hart, J. Pines, G. Haller, S.M. Gruner, H.T. Philipp, M.W. Tate, M. Hromalik, L.J. Koerner, N. van Bakel, J. Morse, W. Ghonsalves, D. Arnlund, M.J. Bogan, C. Caleman, R. Fromme, C.Y. Hampton, M.S. Hunter, L.C. Johansson, G. Katona, C. Kupitz, M. Liang, A.V. Martin, K. Nass, L. Redecke, F. Stellato, N. Timneanu, D. Wang, N.A. Zatsepin, D. Schafer, J. Defever, R. Neutze, P. Fromme, J.C. Spence, H.N. Chapman, I. Schlichting, High-Resolution Protein Structure Determination by Serial Femtosecond Crystallography. Science 337, 362–364 (2012)

    Google Scholar 

  • M. Caffrey, C. Porter, Crystallizing membrane proteins for structure determination using lipidic mesophases (2010). http://www.jove.com/video/1712/ crystallizing-membrane-proteins-for-structure-determination-using

  • L.M. Chavas, Y. Yamada, M. Hiraki, N. Igarashi, N. Matsugaki, S. Wakatsuki, UV LED lighting for automated crystal centring. J Synchrotron Radiat. 18, 11–15 (2011)

    Article  Google Scholar 

  • H.N. Chapman, A. Barty, M.J. Bogan, S. Boutet, M. Frank, S.P. Hau-Riege, S. Marchesini, B.W. Woods, S.C. Bajt, W.H. Benner, R.A. London, E. Plönjes, M. Kuhlmann, R. Treusch, S. Düsterer, T. Tschentscher, J.R. Schneider, E. Spiller, T. Möller, C. Bostedt, M. Hoener, D.A. Shapiro, K.O. Hodgson, D. van der Spoel, F. Burmeister, M. Bergh, C. Caleman, G. Huldt, M.M. Seibert, Maia FRNC, R.W. Lee, A. Szöke, N. Timneanu, J. Hajdu, Femtosecond diffractive imaging with a soft-X-ray free-electron laser. Nat. Phys. 2, 839–843 (2006)

    Google Scholar 

  • H.N. Chapman, P. Fromme, A. Barty, T.A. White, R.A. Kirian, A. Aquila, M.S. Hunter, J. Schulz, D.P. DePonte, U. Weierstall, R.B. Doak, F.R. Maia, A.V. Martin, I. Schlichting, L. Lomb, N. Coppola, R.L. Shoeman, S.W. Epp, R. Hartmann, D. Rolles, A. Rudenko, L. Foucar, N. Kimmel, G. Weidenspointner, P. Holl, M. Liang, M. Barthelmess, C. Caleman, S. Boutet, M.J. Bogan, J. Krzywinski, C. Bostedt, S. Bajt, L. Gumprecht, B. Rudek, B. Erk, C. Schmidt, A. Hömke, C. Reich, D. Pietschner, L. Strüder, G. Hauser, H. Gorke, J. Ullrich, S. Herrmann, G. Schaller, F. Schopper, H. Soltau, K.U. Kühnel, M. Messerschmidt, J.D. Bozek, S.P. Hau-Riege, M. Frank, C.Y. Hampton, R.G. Sierra, D. Starodub, G.J. Williams, J. Hajdu, N. Timneanu, M.M. Seibert, J. Andreasson, A. Rocker, O. Jönsson, M. Svenda, S. Stern, K. Nass, R. Andritschke, C.D. Schröter, F. Krasniqi, M. Bott, K.E. Schmidt, X. Wang, I. Grotjohann, J.M. Holton, T.R. Barends, R. Neutze, S. Marchesini, R. Fromme, S. Schorb, D. Rupp, M. Adolph, T. Gorkhover, I. Andersson, H. Hirsemann, G. Potdevin, H. Graafsma, B. Nilsson, J.C. Spence, Femtosecond X-ray protein nanocrystallography. Nature 470, 73–77 (2011)

    Google Scholar 

  • A.E. Cohen, S.M. Soltis, A. Gonz´alez, L. Aguila, R. Alonso-Mori, C.O. Barnes, E.L. Baxter, W. Brehmer, A.S. Brewster, A.T. Brunger, G. Calero, J.F. Chang, M. Chollet, P. Ehrensberger, T.L. Eriksson, Y. Feng, J. Hattne, B. Hedman, M. Hollenbeck, J.M. Holton, S. Keable, B.K. Kobilka, E.G. Kovaleva, A.C. Kruse, H.T. Lemke, G. Lin, A.Y. Lyubimov, A. Manglik, I.I. Mathews, S.E. McPhillips, S. Nelson, J.W. Peters, N.K. Sauter, C.A. Smith, J. Song, H.P. Stevenson, Y. Tsai, M. Uervirojnangkoorn, V. Vinetsky, S. Wakatsuki, W.I. Weis, O.A. Zadvornyy, O.B. Zeldin, D. Zhu, K.O. Hodgson, Goniometer-based femtosecond crystallography with X-ray free electron lasers. Proc. Natl. Acad. Sci. U. S. A. 111, 17122–17127 (2014)

    Google Scholar 

  • J.P. Colletier, A. Royant, A. Specht, B. Sanson, F. Nachon, P. Masson, G. Zaccai, J.L. Sussman, M. Goeldner, I. Silman, D. Bourgeois, M. Weik, Use of a ’caged’ analogue to study the traffic of choline within acetylcholinesterase by kinetic crystallography. Acta Crystallogr. D Biol. Crystallogr. 63, 1115–1128 (2007)

    Article  Google Scholar 

  • C.E. Conrad, S. Basu, D. James, D. Wang, A. Schaffer, S. Roy-Chowdhury, N.A. Zatsepin, A. Aquila, J. Coe, C. Gati, M.S. Hunter, J.E. Koglin, C. Kupitz, G. Nelson, G. Subramanian, T.A. White, Y. Zhao, J. Zook, S. Boutet, V. Cherezov, J.C. Spence, R. Fromme, U. Weierstall, P. Fromme, A novel inert crystal delivery medium for serial femtosecond crystallography. IUCrJ. 2, 421–430 (2015)

    Article  Google Scholar 

  • G. David, J. P´erez, Combined sampler robot and high-performance liquid chromatography: a fully automated system for biological small-angle X-ray scattering experiments at the Synchrotron SOLEIL SWING beamline. J. Appl. Crystallogr. 42, 892–900 (2009)

    Google Scholar 

  • M.C. Deller, B. Rupp, Approaches to automated protein crystal harvesting. Acta Crystallogr. F Struct. Biol. Commun. 70, 133–155 (2014)

    Article  Google Scholar 

  • M.D. de Jonge, S. Vogt, Hard X-ray fluorescence tomography–an emerging tool for structural visualization. Curr. Opin. Struct. Biol. 20, 606–614 (2010)

    Article  Google Scholar 

  • D. Deng, P.C. Sun, C.Y. Yan, M. Ke, X. Jiang, L. Xiong, W. Ren, K. Hirata, M. Yamamoto, S. Fan, N. Yan, Molecular basis of ligand recognition and transport by glucose transporters. Nature (2015). doi:10.1038/nature14655. [Epub ahead of print]

    Google Scholar 

  • D.P. DePonte, U. Weierstall, K. Schmidt, J. Warner, D. Starodub, J.C.H. Spence, R.B. Doak, Gas dynamic virtual nozzle for generation of microscopic droplet streams. J. Phys. D-Appl. Phys. 41, 195505 (2008). doi:10.1088/0022-3727/41/19/195505

    Article  ADS  Google Scholar 

  • S. Desbois, S.A. Seabrook, J. Newman, Some practical guidelines for UV imaging in the protein crystallization laboratory. Acta Crystallogr. Sect. F Struct. Biol Crystallogr. Commun. 69, 201–208 (2013)

    Article  Google Scholar 

  • O. Duss, M. Yulikov, G. Jeschke, F.H. Allain, EPR-aided approach for solution structure determination of large RNAs or protein-RNA complexes. Nat. Commun. 5, 3669 (2014)

    Article  ADS  Google Scholar 

  • G. Evans, D. Axford, D. Waterman, R.L. Owen, Macromolecular microcrystallography. Crystallogr. Rev. 17, 105–142 (2011)

    Article  Google Scholar 

  • M. Frank, D.B. Carlson, M.S. Hunter, G.J. Williams, M. Messerschmidt, N.A. Zatsepin, A. Barty, W.H. Benner, K. Chu, A.T. Graf, S.P. Hau-Riege, R.A. Kirian, C. Padeste, T. Pardini, B. Pedrini, B. Segelke, M.M. Seibert, J.C. Spence, C.J. Tsai, S.M. Lane, X.D. Li, G. Schertler, S. Boutet, M. Coleman, J.E. Evans, Femtosecond X-ray diffraction from two-dimensional protein crystals. IUCrJ. 1, 95–100 (2014)

    Article  Google Scholar 

  • M.A. Graewert, D. Franke, C.M. Jeffries, C.E. Blanchet, D. Ruskule, K. Kuhle, A. Flieger, B. Schäfer, B. Tartsch, R. Meijers, D.I. Svergun, Automated pipeline for purification, biophysical and x-ray analysis of biomacromolecular solutions. Sci. Rep. 5, 10734 (2015)

    Article  ADS  Google Scholar 

  • L. Galli, Phasing using high intensity free-electron laser radiation. Doctoral Dissertation, University of Hamburg, 2014

    Google Scholar 

  • L. Galli, S.K. Son, T.A. White, R. Santra, H.N. Chapman, M.H. Nanao, Towards RIP using free-electron laser SFX data. J. Synchrotron Radiat. 22, 249–255 (2015)

    Article  Google Scholar 

  • C. Gati, G. Bourenkov, M. Klinge, D. Rehders, F. Stellato, D. Oberthür, O. Yefanov, B.P. Sommer, S. Mogk, M. Duszenko, C. Betzel, T.R. Schneider, H.N. Chapman, L. Redecke, Serial crystallography on in vivo grown microcrystals using synchrotron radiation. IUCrJ. 1, 87–94 (2014)

    Article  Google Scholar 

  • H.M. Ginn, A.S. Brewster, J. Hattne, G. Evans, A. Wagner, J.M. Grimes, N.K. Sauter, G. Sutton, D.I. Stuart, A revised partiality model and post-refinement algorithm for X-ray free-electron laser data. Acta Crystallogr. D Biol. Crystallogr. 71(Pt 6), 1400–1410 (2015)

    Article  Google Scholar 

  • H. Hara, T. Tanaka, T. Tanabe, X.-M. Mar´echal, S. Okada, H. Kitamura, In-vacuum undulators of SPring-8. J. Synchrotron Radiat. 5, 403–405 (1998)

    Google Scholar 

  • J. Hattne, N. Echols, R. Tran, J. Kern, R.J. Gildea, A.S. Brewster, R. Alonso-Mori, C. Glöckner, J. Hellmich, H. Laksmono, R.G. Sierra, B. Lassalle-Kaiser, A. Lampe, G. Han, S. Gul, D. DiFiore, D. Milathianaki, A.R. Fry, A. Miahnahri, W.E. White, D.W. Schafer, M.M. Seibert, J.E. Koglin, D. Sokaras, T.C. Weng, J. Sellberg, M.J. Latimer, P. Glatzel, P.H. Zwart, R.W. Grosse-Kunstleve, M.J. Bogan, M. Messerschmidt, G.J. Williams, S. Boutet, J. Messinger, A. Zouni, J. Yano, U. Bergmann, V.K. Yachandra, P.D. Adams, N.K. Sauter, Accurate macromolecular structures using minimal measurements from X-ray free-electron lasers. Nat. Methods 11, 545–548 (2014)

    Google Scholar 

  • R. Henderson, Cryo-protection of protein crystals against radiation damage in electron and x-ray radiation. Proc. R. Soc. Lond. 241, 6–8 (1990)

    Article  ADS  Google Scholar 

  • K. Hirata, Y. Kawano, G. Ueno, K. Hashimoto, H. Murakami, K. Hasegawa, T. Hikima, T. Kumasaka, M. Yamamoto, Achievement of protein micro-crystallography at SPring-8 beamline BL32XU. J. Phys. Conf. Ser. 425, 012002 (2013)

    Article  ADS  Google Scholar 

  • K. Hirata, K. Shinzawa-Itoh, N. Yano, S. Takemura, K. Kato, M. Hatanaka, K. Muramoto, T. Kawahara, T. Tsukihara, E. Yamashita, K. Tono, G. Ueno, T. Hikima, H. Murakami, Y. Inubushi, M. Yabashi, T. Ishikawa, M. Yamamoto, T. Ogura, H. Sugimoto, J.R. Shen, S. Yoshikawa, H. Ago, Determination of damage-free crystal structure of an X-ray-sensitive protein using an XFEL. Nat. Methods 11, 734–736 (2014)

    Article  Google Scholar 

  • K.C. Holmes, D. Popp, W. Gebhard, W. Kabsch, Atomic model of the actin filament. Nature 347, 44–49 (1990)

    Article  ADS  Google Scholar 

  • M.S. Hunter, B. Segelke, M. Messerschmidt, G.J. Williams, N.A. Zatsepin, A. Barty, W.H. Benner, D.B. Carlson, M. Coleman, A. Graf, S.P. Hau-Riege, T. Pardini, M.M. Seibert, J. Evans, S. Boutet, M. Frank, Fixed-target protein serial microcrystallography with an x-ray free electron laser. Sci Rep. 4, 6026 (2014)

    Article  ADS  Google Scholar 

  • G. Jeschke, DEER distance measurements on proteins. Ann. Rev. Phys. Chem. 63, 419–446 (2012)

    Article  ADS  Google Scholar 

  • W. Kabsch, Processing of X-ray snapshots from crystals in random orientations. Acta Crystallogr. D Biol. Crystallogr. 70, 2204–2216 (2014)

    Article  Google Scholar 

  • Z. Kam, Determination of macromolecular structure in solution by spatial correlation of scattering fluctuations. Macromolecules 10, 927–934 (1977)

    Article  ADS  Google Scholar 

  • Z. Kam, M.H.J. Koch, J. Bordas, Fluctuation x-ray scattering from biological particles in frozen solution by using synchrotron radiation. PNAS 78, 3559–3562 (1981)

    Article  ADS  Google Scholar 

  • Y. Kang, X.E. Zhou, X. Gao, Y. He, W. Liu, A. Ishchenko, A. Barty, T.A. White, O. Yefanov, G.W. Han, Q. Xu, P.W. de Waal, J. Ke, M.H. Tan, C. Zhang, A. Moeller, G.M. West, B.D. Pascal, N. Van Eps, L.N. Caro, S.A. Vishnivetskiy, R.J. Lee, K.M. Suino-Powell, X. Gu, K. Pal, J. Ma, X. Zhi, S. Boutet, G.J. Williams, M. Messerschmidt, C. Gati, N.A. Zatsepin, D. Wang, D. James, S. Basu, S. Roy-Chowdhury, C.E. Conrad, J. Coe, H. Liu, S. Lisova, C. Kupitz, I. Grotjohann, R. Fromme, Y. Jiang, M. Tan, H. Yang, J. Li, M. Wang, Z. Zheng, D. Li, N. Howe, Y. Zhao, J. Standfuss, K. Diederichs, Y. Dong, C.S. Potter, B. Carragher, M. Caffrey, H. Jiang, H.N. Chapman, J.C. Spence, P. Fromme, U. Weierstall, O.P. Ernst, V. Katritch, V.V. Gurevich, P.R. Griffin, W.L. Hubbell, R.C. Stevens, V. Cherezov, K. Melcher, H.E. Xu, Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature 523, 561–567 (2015)

    Google Scholar 

  • J. Kern, R. Alonso-Mori, J. Hellmich, R. Tran, J. Hattne, H. Laksmono, C. Glöckner, N. Echols, R.G. Sierra, J. Sellberg, B. Lassalle-Kaiser, R.J. Gildea, P. Glatzel, R.W. Grosse-Kunstleve, M.J. Latimer, T.A. McQueen, D. DiFiore, A.R. Fry, M. Messerschmidt, A. Miahnahri, D.W. Schafer, M.M. Seibert, D. Sokaras, T.C. Weng, P.H. Zwart, W.E. White, P.D. Adams, M.J. Bogan, S. Boutet, G.J. Williams, J. Messinger, N.K. Sauter, A. Zouni, U. Bergmann, J. Yano, V.K. Yachandra, Room temperature femtosecond X-ray diffraction of photosystem II microcrystals. Proc. Natl. Acad. Sci. U. S. A. 109, 9721–9726 (2012)

    Google Scholar 

  • A. le Maire, M. Gelin, S. Pochet, F. Hoh, M. Pirocchi, J.F. Guichou, J.L. Ferrer, G. Labesse, In-plate protein crystallization, in situ ligand soaking and X-ray diffraction. Acta Crystallogr. D Biol. Crystallogr. 67, 747–755 (2011)

    Article  Google Scholar 

  • M. Levantino, G. Schiro, H.T. Lemke, G. Cottone, J.M. Glownia, D. Zhu, M. Chollet, H. Ihee, A. Cupanem, M. Cammarata, Ultrafast myoglobin structural dynamics observed with an X-ray free-electron laser. Nat. Commun. 6, 6772 (2015)

    Article  ADS  Google Scholar 

  • Q. Liu, T. Dahmane, Z. Zhang, Z. Assur, J. Brasch, L. Shapiro, F. Mancia, W.A. Hendrickson, Structures from anomalous diffraction of native biological macromolecules. Science 336, 1033–1037 (2012)

    Article  ADS  Google Scholar 

  • H. Liu, B.K. Poon, D.K. Saldin, J.C. Spence, P.H. Zwart, Three-dimensional single-particle imaging using angular correlations from X-ray laser data. Acta Crystallogr. A 69, 365–373 (2013)

    Article  MathSciNet  Google Scholar 

  • W. Liu, D. Wacker, C. Gati, G.W. Han, D. James, D. Wang, G. Nelson, U. Weierstall, V. Katritch, A. Barty, N.A. Zatsepin, D. Li, M. Messerschmidt, S. Boutet, G.J. Williams, J.E. Koglin, M.M. Seibert, C. Wang, S.T. Shah, S. Basu, R. Fromme, C. Kupitz, K.N. Rendek, I. Grotjohann, P. Fromme, R.A. Kirian, K.R. Beyerlein, T.A. White, H.N. Chapman, M. Caffrey, J.C. Spence, R.C. Stevens, V. Cherezov, Serial femtosecond Crystallography of G protein–coupled receptors. Science 342, 1521–1524 (2013)

    Article  ADS  Google Scholar 

  • Q. Liu, Y. Guo, Y. Chang, Z. Cai, Z. Assur, F. Mancia, M.I. Greene, W.A. Hendrickson, Multi-crystal native SAD analysis at 6 keV. Acta Crystallogr. D Biol. Crystallogr. 70, 2544–2557 (2014)

    Article  Google Scholar 

  • N.T. Loh, V. Elser, Reconstruction algorithm for single-particle diffraction imaging experiments. Phys. Rev. E Stat. Nonlinear Soft Matter Phys. 80, 026705 (2009)

    Article  ADS  Google Scholar 

  • A.A. Lutman, F.J. Decker, J. Arthur, M. Chollet, Y. Feng, J. Hastings, Z. Huang, H. Lemke, H.D. Nuhn, A. Marinelli, J.L. Turner, S. Wakatsuki, J. Welch, D. Zhu, Demonstration of single-crystal self-seeded two-color x-ray free-electron lasers. Phys Rev Lett. 113, 254801 (2014)

    Article  ADS  Google Scholar 

  • A.Y. Lyubimov, T.D. Murray, A. Koehl, I.E. Araci, M. Uervirojnangkoorn, O.B. Zeldin, A.E. Cohen, S.M. Soltis, E.L. Baxter, A.S. Brewster, N.K. Sauter, A.T. Brunger, J.M. Berger, Capture and X-ray diffraction studies of protein microcrystals in a microfluidic trap array. Acta Crystallogr. D Biol. Crystallogr. 71, 928–940 (2015)

    Article  Google Scholar 

  • J.T. Madden, E.L. DeWalt, G.J. Simpson, Two-photon excited UV fluorescence for protein crystal detection. Acta Crystallogr. D Biol. Crystallogr. 67, 839–846 (2011)

    Article  Google Scholar 

  • J.T. Madden, S.J. Toth, C.M. Dettmar, J.A. Newman, R.A. Oglesbee, H.G. Hedderich, R.M. Everly, M. Becker, J.A. Ronau, S.K. Buchanan, V. Cherezov, M.E. Morrow, S. Xu, D. Ferguson, O. Makarov, C. Das, R. Fischetti, G.J. Simpson, Integrated nonlinear optical imaging microscope for on-axis crystal detection and centering at a synchrotron beamline. J Synchrotron Radiat. 20, 531–540 (2013)

    Article  Google Scholar 

  • E. Malmerberg, C.A. Kerfeld, P.H. Zwart, Operational properties of fluctuation X-ray scattering data. IUCrJ. 2, 309–316 (2015)

    Article  Google Scholar 

  • A. Marinelli, D. Ratner, A.A. Lutman, J. Turner, J. Welch, F.J. Decker, H. Loos, C. Behrens, S. Gilevich, A.A. Miahnahri, S. Vetter, T.J. Maxwell, Y. Ding, R. Coffee, S. Wakatsuki, Z. Huang, High-intensity double-pulse X-ray free-electron laser. Nat. Commun. 6, 6369 (2015)

    Article  ADS  Google Scholar 

  • A. Martel, P. Liu, T.M. Weiss, M. Niebuhr, H. Tsuruta, An integrated high-throughput data acquisition system for biological solution X-ray scattering studies. J. Synchrotron Radiat. 19, 431–434 (2012)

    Article  Google Scholar 

  • D. Mendez, T.J. Lane, J. Sung, J. Sellberg, C. Levard, H. Watkins, A.E. Cohen, M. Soltis, S. Sutton, J. Spudich, V. Pande, D. Ratner, S. Doniach, Observation of correlated X-ray scattering at atomic resolution. Philos. Trans. R. Soc. Lond. B Biol. Sci. 369, 20130315 (2014)

    Article  Google Scholar 

  • M. Møller, S.S. Nielsen, S. Ramachandran, Y. Li, G. Tria, W. Streicher, M.V. Petoukhov, R.A. Cerione, R.E. Gillilan, B. Vestergaard, Small angle X-ray scattering studies of mitochondrial glutaminase C reveal extended flexible regions, and link oligomeric state with enzyme activity. PLoS One 8, e74783 (2013)

    Article  ADS  Google Scholar 

  • J.W. Murray, E. Garman, R. Ravelli, X-ray absorption by macromolecular crystals: the effects of wavelength and crystal composition on absorbed dose. J. Appl. Crystallogr. 37, 513–522 (2004)

    Article  Google Scholar 

  • P. Nogly, D. James, D. Wang, T.A. White, N. Zatsepin, A. Shilova, G. Nelson, H. Liu, L. Johansson, M. Heymann, K. Jaeger, M. Metz, C. Wickstrand, W. Wu, P. Båth, P. Berntsen, D. Oberthuer, V. Panneels, V. Cherezov, H. Chapman, G. Schertler, R. Neutze, J. Spence, I. Moraes, M. Burghammer, J. Standfuss, U. Weierstall, Lipidic cubic phase serial millisecond crystallography using synchrotron radiation. IUCrJ. 2(Pt 2), 168–176 (2015)

    Article  Google Scholar 

  • R.L. Owen, E. Rudi˜no-Pi˜nera, E.F. Garman, Experimental determination of the radiation dose limit for cryocooled protein crystals. Proc. Natl. Acad. Sci. U. S. A. 103, 4912–4917 (2006)

    Google Scholar 

  • R.L. Owen, D. Axford, J.E. Nettleship, R.J. Owens, J.I. Robinson, A.W. Morgan, A.S. Dor´e, G. Lebon, C.G. Tate, E.E. Fry, J. Ren, D.I. Stuart, G. Evans, Outrunning free radicals in room-temperature macromolecular crystallography. Acta Crystallogr. D Biol. Crystallogr. 68, 810–818 (2012)

    Google Scholar 

  • R.L. Owen, N. Paterson, D. Axford, J. Aishima, C. Schulze-Briese, J. Ren, E.E. Fry, D.I. Stuart, G. Evans, Exploiting fast detectors to enter a new dimension in room-temperature crystallography. Acta Crystallogr. D Biol. Crystallogr. 70, 1248–1256 (2014)

    Article  Google Scholar 

  • A. Perrakis, F. Cipriani, J.C. Castagna, L. Claustre, M. Burghammer, C. Riekel, S. Cusack, Protein microcrystals and the design of a microdiffractometer: current experience and plans at EMBL and ESRF/ID13. Acta Crystallogr. D Biol. Crystallogr. 55, 1765–1770 (1999)

    Article  Google Scholar 

  • A. Round, F. Felisaz, L. Fodinger, A. Gobbo, J. Huet, C. Villard, C.E. Blanchet, P. Pernot, S. McSweeney, M. Roessle, D.I. Svergun, F. Cipriani, BioSAXS Sample Changer: a robotic sample changer for rapid and reliable high-throughput X-ray solution scattering experiments. Acta Crystallogr. D Biol. Crystallogr. 71, 67–75 (2015)

    Article  Google Scholar 

  • M.V. Petoukhov, D.I. Svergun, Ambiguity assessment of small-angle scattering curves from monodisperse systems. Acta Crystallogr. D 71, 1051–1058 (2015)

    Article  Google Scholar 

  • G. Rosenbaum, K.C. Holmes, J. Witz, Synchrotron radiation as a source for X-ray diffraction. Nature 230, 434–437 (1971)

    Article  ADS  Google Scholar 

  • C.G. Roessler, A. Kuczewski, R. Stearns, R. Ellson, J. Olechno, A.M. Orville, M. Allaire, A.S. Soares, A. H´eroux, Acoustic methods for high-throughput protein crystal mounting at next-generation macromolecular crystallographic beamlines. J. Synchrotron Radiat. 20, 805–808 (2013)

    Google Scholar 

  • T. Saio, K. Ogura, M. Yokochi, Y. Kobashigawa, F. Inagaki, Two-point anchoring of a lanthanide-binding peptide to a target protein enhances the paramagnetic anisotropic effect. J. Biomol. NMR 44, 157–166 (2009)

    Article  Google Scholar 

  • T. Saio, X. Guan, P. Rossi, A. Economou, C.G. Kalodimos, Structural basis for protein antiaggregation activity of the trigger factor chaperone. Science 344, 1250494 (2014)

    Article  Google Scholar 

  • D.K. Saldin, H.C. Poon, M.J. Bogan, S. Marchesini, D.A. Shapiro, R.A. Kirian, U. Weierstall, J.C. Spence, New light on disordered ensembles: ab initio structure determination of one particle from scattering fluctuations of many copies. Phys. Rev. Lett. 106, 115501 (2011)

    Article  ADS  Google Scholar 

  • N.K. Sauter, J. Hattne, R.W. Grosse-Kunstleve, N. Echols, New Python-based methods for data processing. Acta Crystallogr. D Biol. Crystallogr. 69, 1274–1282 (2013)

    Article  Google Scholar 

  • N.K. Sauter, J. Hattne, A.S. Brewster, N. Echols, P.H. Zwart, P.D. Adams, Improved crystal orientation and physical properties from single-shot XFEL stills. Acta Crystallogr. D Biol. Crystallogr. 70, 3299–3309 (2014)

    Article  Google Scholar 

  • M.R. Sawaya, S. Sambashivan, R. Nelson, M.I. Ivanova, S.A. Sievers, M.I. Apostol, M.J. Thompson, M. Balbirnie, J.J. Wiltzius, H.T. McFarlane, A.Ø. Madsen, C. Riekel, D. Eisenberg, Atomic structures of amyloid cross-beta spines reveal varied steric zippers. Nature 447, 453–457 (2007)

    Article  ADS  Google Scholar 

  • M. Schmidt, Mix and inject: reaction initiation by diffusion for time-resolved macromolecular crystallography. Adv. Condens. Matter Phys. 2013, Article ID 167276, 10 pages (2013). http://dx.doi.org/10.1155/2013/167276

  • R.G. Sierra, H. Laksmono, J. Kern, R. Tran, J. Hattne, R. Alonso-Mori, B. Lassalle-Kaiser, C. Glöckner, J. Hellmich, D.W. Schafer, N. Echols, R.J. Gildea, R.W. Grosse-Kunstleve, J. Sellberg, T.A. McQueen, A.R. Fry, M.M. Messerschmidt, A. Miahnahri, M.M. Seibert, C.Y. Hampton, D. Starodub, N.D. Loh, D. Sokaras, T.C. Weng, P.H. Zwart, P. Glatzel, D. Milathianaki, W.E. White, P.D. Adams, G.J. Williams, S. Boutet, A. Zouni, J. Messinger, N.K. Sauter, U. Bergmann, J. Yano, V.K. Yachandra, M.J. Bogan, Nanoflow electrospinning serial femtosecond crystallography. Acta Crystallogr. D68, 1584–1587 (2012)

    Google Scholar 

  • M. Skou, S. Skou, T.G. Jensen, B. Vestergaard, R.E. Gillilan, In situ microfluidic dialysis for biological small-angle X-ray scattering. J. Appl. Crystallogr. 47, 1355–1366 (2014)

    Article  Google Scholar 

  • J.L. Smith, R.F. Fischetti, M. Yamamoto, Micro-crystallography comes of age. Curr. Opin. Struct. Biol. 22, 602–612 (2012)

    Article  Google Scholar 

  • A.S. Soares, M.A. Engel, R. Stearns, S. Datwani, J. Olechno, R. Ellson, J.M. Skinner, M. Allaire, A.M. Orville, Acoustically mounted microcrystals yield high-resolution X-ray structures. Biochemistry 50, 4399–4401 (2011)

    Article  Google Scholar 

  • S.K. Son, H.N. Chapman, R. Santra, Multiwavelength anomalous diffraction at high x-ray intensity. Phys. Rev. Lett. 107, 218102 (2011)

    Article  ADS  Google Scholar 

  • H.P. Stevenson, A.M. Makhov, M. Calero, A.L. Edwards, O.B. Zeldin, I.I. Mathews, G. Lin, C.O. Barnes, H. Santamaria, T.M. Ross, S.M. Soltis, C. Khosla, V. Nagarajan, J.F. Conway, A.E. Cohen, G. Calero, Use of transmission electron microscopy to identify nanocrystals of challenging protein targets. Proc. Natl. Acad. Sci. U. S. A. 111, 8470–8475 (2014a)

    Article  ADS  Google Scholar 

  • H.P. Stevenson, D.P. DePonte, A.M. Makhov, J.F. Conway, O.B. Zeldin, S. Boutet, G. Calero, A.E. Cohen, Transmission electron microscopy as a tool for nanocrystal characterization pre- and post-injector. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 369, 20130322 (2014b)

    Article  Google Scholar 

  • M. Suga, F. Akita, K. Hirata, G. Ueno, H. Murakami, Y. Nakajima, T. Shimizu, K. Yamashita, M. Yamamoto, H. Ago, J.R. Shen, Native structure of photosystem II at 1.95 Å resolution viewed by femtosecond X-ray pulses. Nature 517, 99–103 (2015)

    Google Scholar 

  • M. Sugahara, E. Mizohata, E. Nango, M. Suzuki, T. Tanaka, T. Masuda, R. Tanaka, T. Shimamura, Y. Tanaka, C. Suno, K. Ihara, D. Pan, K. Kakinouchi, S. Sugiyama, M. Murata, T. Inoue, K. Tono, C. Song, J. Park, T. Kameshima, T. Hatsui, Y. Joti, M. Yabashi, S. Iwata, Grease matrix as a versatile carrier of proteins for serial crystallography. Nat. Methods 12, 61–63 (2015)

    Article  Google Scholar 

  • J. Tenboer, S. Basu, N. Zatsepin, K. Pande, D. Milathianaki, M. Frank, M. Hunter, S. Boutet, G.J. Williams, J.E. Koglin, D. Oberthuer, M. Heymann, C. Kupitz, C. Conrad, J. Coe, S. Roy-Chowdhury, U. Weierstall, D. James, D. Wang, T. Grant, A. Barty, O. Yefanov, J. Scales, C. Gati, C. Seuring, V. Srajer, R. Henning, P. Schwander, R. Fromme, A. Ourmazd, K. Moffat, J.J. Van Thor, J.C. Spence, P. Fromme, H.N. Chapman, M. Schmidt, Time-resolved serial crystallography captures high-resolution intermediates of photoactive yellow protein. Science 346, 1242–1246 (2014)

    Google Scholar 

  • T. Terai, E. Maki, S. Sugiyama, Y. Takahashi, H. Matsumura, Y. Mori, T. Nagano, Rational development of caged-biotin protein-labeling agents and some applications in live cells. Chem. Biol. 18, 1261–1272 (2011)

    Article  Google Scholar 

  • K. Tono, E. Nango, M. Sugahara, C. Song, J. Park, T. Tanaka, R. Tanaka, Y. Joti, T. Kameshima, S. Ono, T. Hatsui, E. Mizohata, M. Suzuki, T. Shimamura, Y. Tanaka, S. Iwata, M. Yabashi, Diverse application platform for hard X-ray diffraction in SACLA (DAPHNIS): application to serial protein crystallography using an X-ray free-electron laser. J Synchrotron Radiat. 22, 532–537 (2015)

    Article  Google Scholar 

  • M. Uervirojnangkoorn, O.B. Zeldin, A.Y. Lyubimov, J. Hattne, A.S. Brewster, N.K. Sauter, A.T. Brunger, W.I. Weis, Enabling X-ray free electron laser crystallography for challenging biological systems from a limited number of crystals. Elife. 4 (2015). doi:10.7554/eLife.05421

    Google Scholar 

  • T. Ursby, M. Weik, E. Fioravanti, M. Delarue, M. Goeldner, D. Bourgeois, Cryophotolysis of caged compounds: a technique for trapping intermediate states in protein crystals. Acta Crystallogr. D Biol. Crystallogr. 58, 607–614 (2002)

    Article  Google Scholar 

  • N. Van Eps, A.M. Preininger, N. Alexander, A.I. Kaya, S. Meier, J. Meiler, H.E. Hamm, W.L. Hubbell, Interaction of a G protein with an activated receptor opens the interdomain interface in the alpha subunit. Proc. Natl. Acad. Sci. U. S. A. 108, 9420–9424 (2011)

    Article  ADS  Google Scholar 

  • R.D. Wampler, D.J. Kissick, C.J. Dehen, E.J. Gualtieri, J.L. Grey, H.F. Wang, D.H. Thompson, J.X. Cheng, G.J. Simpson, Selective detection of protein crystals by second harmonic microscopy. J. Am. Chem. Soc. 130, 14076–14077 (2008)

    Article  Google Scholar 

  • W. Wan, H. Wille, J. Stöhr, A. Kendall, W. Bian, M. McDonald, S. Tiggelaar, J.C. Watts, S.B. Prusiner, G. Stubbs, Structural studies of truncated forms of the prion protein PrP. Biophys. J. 108, 1548–1554 (2015)

    Article  ADS  Google Scholar 

  • N. Watanabe, H. Murai, I. Tanaka, Semi-automatic protein crystallization system that allows in situ observation of X-ray diffraction from crystals in the drop. Acta Crystallogr. D Biol. Crystallogr. 58, 1527–1530 (2002)

    Article  Google Scholar 

  • U. Weierstall, D. James, C. Wang, T.A. White, D. Wang, W. Liu, J.C. Spence, R. Bruce Doak, G. Nelson, P. Fromme, R. Fromme, I. Grotjohann, C. Kupitz, N.A. Zatsepin, H. Liu, S. Basu, D. Wacker, G.W. Han, V. Katritch, S. Boutet, M. Messerschmidt, G.J. Williams, J.E. Koglin, M. Marvin Seibert, M. Klinker, C. Gati, R.L. Shoeman, A. Barty, H.N. Chapman, R.A. Kirian, K.R. Beyerlein, R.C. Stevens, D. Li, S.T. Shah, N. Howe, M. Caffrey, V. Cherezov, Nat. Commun. 5, 3309 (2014)

    Article  ADS  Google Scholar 

  • M.S. Weiss, G. Mander, R. Hedderich, K. Diederichs, U. Ermler, E. Warkentin, Determination of a novel structure by a combination of long-wavelength sulfur phasing and radiation-damage-induced phasing. Acta Crystallogr. D Biol. Crystallogr. 60, 686–695 (2004)

    Article  Google Scholar 

  • T.A. White, R.A. Kirian, A.V. Martin, A. Aquila, K. Nass, A. Barty, H.N. Chapman, CrystFEL: a software suite for snapshot serial crystallography J. Appl. Crystallogr. 45, 335–341 (2012)

    Article  Google Scholar 

  • T.A. White, A. Barty, F. Stellato, J.M. Holton, R.A. Kirian, N.A. Zatsepin, H.N. Chapman, Crystallographic data processing for free-electron laser sources. Acta Crystallogr. D Biol. Crystallogr. 69, 1231–1240 (2013)

    Article  Google Scholar 

  • B. Xiao, S.J. Smerdon, D.H. Jones, G.G. Dodson, Y. Soneji, A. Aitken, S.J. Gamblin, Structure of a 14-3-3 protein and implications for coordination of multiple signalling pathways. Nature 376, 188–191 (1995)

    Article  ADS  Google Scholar 

  • H. Zhang, H. Unal, C. Gati, G.W. Han, W. Liu, N.A. Zatsepin, D. James, D. Wang, G. Nelson, U. Weierstall, M.R. Sawaya, Q. Xu, M. Messerschmidt, G.J. Williams, S. Boutet, O.M. Yefanov, T.A. White, C. Wang, A. Ishchenko, K.C. Tirupula, R. Desnoyer, J. Coe, C.E. Conrad, P. Fromme, R.C. Stevens, V. Katritch, S.S. Karnik, V. Cherezov, Structure of the Angiotensin receptor revealed by serial femtosecond crystallography. Cell 161, 833–844 (2015)

    Article  Google Scholar 

  • Q. Zhou, Y. Lai, T. Bacaj, M. Zhao, A.Y. Lyubimov, M. Uervirojnangkoorn, O.B. Zeldin, A.S. Brewster, N.K. Sauter, A.E. Cohen, S.M. Soltis, R. Alonso-Mori, M. Chollet, H.T. Lemke, R.A. Pfuetzner, U.B. Choi, W.I. Weis, J. Diao, T.C. Sudhof, A.T. Brunger, Architecture of the synaptotagmin-SNARE machinery for neuronal exocytosis. Nature 525, 62–67 (2015)

    Article  Google Scholar 

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Acknowledgements

The author is deeply indebted to Profs. Jochen Schneider and Jerome Hastings for their encouragements throughout the process, is grateful for fruitful discussions with the colleagues at SLAC and Stanford University, in particular to Marc Deller, Sebastien Boutet, Han Dao, Fatemeh Jabbarpour and Varun Bhadkamkar for their help with editing of the manuscript, and NIH-NIGMS, DOE BES and BER, SLAC and Stanford University for funding.

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Wakatsuki, S. (2015). Structural Biology Applications of Synchrotron Radiation and X-Ray Free-Electron Lasers. In: Jaeschke, E., Khan, S., Schneider, J., Hastings, J. (eds) Synchrotron Light Sources and Free-Electron Lasers. Springer, Cham. https://doi.org/10.1007/978-3-319-04507-8_44-1

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    The SACLA X-Ray Free-Electron Laser Based on Normal-Conducting C-Band Technology
    Published:
    25 January 2016

    DOI: https://doi.org/10.1007/978-3-319-04507-8_9-2

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    DOI: https://doi.org/10.1007/978-3-319-04507-8_49-2

  3. Structural Biology Applications of Synchrotron Radiation and X-Ray Free-Electron Lasers
    Published:
    16 September 2015

    DOI: https://doi.org/10.1007/978-3-319-04507-8_44-1

  4. Original

    The SACLA X-Ray FEL Based on Normal-Conducting C-Band Technology
    Published:
    09 May 2015

    DOI: https://doi.org/10.1007/978-3-319-04507-8_9-1