Abstract
The intense X-ray pulses from free-electron lasers, of only femtoseconds duration, outrun most of the processes that lead to structural degradation in X-ray exposures of macromolecules. Using these sources it is therefore possible to increase the dose to macromolecular crystals by several orders of magnitude higher than usually tolerable in conventional measurements, allowing crystal size to be decreased dramatically in diffraction measurements and without the need to cool the sample. Such pulses lead to the eventual vaporization of the sample, which has required a measurement approach, called serial crystallography, of consolidating snapshot diffraction patterns of many individual crystals. This in turn has further separated the connection between dose and obtainable diffraction information, with the only requirement from a single pattern being that to give enough information to place it, in three-dimensional reciprocal space, in relation to other patterns. Millions of extremely weak patterns can be collected and combined in this way, requiring methods to rapidly replenish the sample into the beam while generating the lowest possible background . The method is suited to time-resolved measurements over timescales below 1 ps to several seconds, and opens new opportunities for phasing. Some straightforward considerations of achievable signal levels are discussed and compared with a wide variety of recent experiments carried out at XFEL, synchrotron, and even laboratory sources, to discuss the capabilities of these new approaches and give some perspectives on their further development.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
McNeil BWJ, Thompson NR (2010) X-ray free-electron lasers. Nat Photon 4:814–821
Liu W, Wacker D, Gati C et al (2013) Serial femtosecond crystallography of G protein-coupled receptors. Science 342:1521–1524
Zhou Q, Lai Y, Bacaj T et al (2015) Architecture of the synaptotagmin-snare machinery for neuronal exocytosis. Nature 525:62–67
DePonte DP, Weierstall U, Schmidt K et al (2008) Gas dynamic virtual nozzle for generation of microscopic droplet streams. J Phys D41:195505
Weierstall U, Spence JCH, Doak RB (2012) Injector for scattering measurements on fully solvated biospecies. Rev Sci Instrum 83:035108
Weierstall U, James D, Wang C et al (2014) Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography. Nat Commun 5:3309
Sugahara M, Mizohata E, Nango E et al (2015) Grease matrix as a versatile carrier of proteins for serial crystallography. Nat Methods 12:61–63
Conrad CE, Basu S, James D et al (2015) A novel inert crystal delivery medium for serial femtosecond crystallography. IUCrJ 2:421–430
Bogan M, Benner W, Boutet S et al (2008) Single particle X-ray diffractive imaging. Nano Lett 8:310–316
Zarrine-Afsar A, Müller C, Talbot FO et al (2011) Self-localizing stabilizing mega-pixel picoliter arrays with size-excluding sorting capabilities. Anal Chem 83:767–773
Hunter MS, Segelke B, Messerschmidt M et al (2014) Fixed-target protein serial microcrystallography with an X-ray free electron laser. Sci Rep 4:6026
Roedig P, Vartiainen I, Duman R et al (2015) A micro-patterned silicon chip as sample holder for macromolecular crystallography experiments with minimal background scattering. Sci Rep 5:10451
Kirian RA, White TA, Holton JM et al (2011) Structure-factor analysis of femtosecond microdiffraction patterns from protein nanocrystals. Acta Crystallogr A 67:131–140
Neutze R, Wouts R, van der Spoel D et al (2000) Potential for biomolecular imaging with femtosecond X-ray pulses. Nature 406:753–757
Huldt G, Szoke A, Hajdu J (2003) Diffraction imaging of single particles and biomolecules. J Struct Biol 144:219–227
Frank M, Carlson DB, Hunter MS et al (2014) Femtosecond X-ray diffraction from two-dimensional protein crystals. IUCrJ 1:95–100
Küpper J, Stern S, Holmegaard L et al (2014) X-ray diffraction from isolated and strongly aligned gas-phase molecules with a free-electron laser. Phys Rev Lett 112:083002
Barends TRM, Foucar L, Ardevol A et al (2015) Direct observation of ultrafast collective motions in co myoglobin upon ligand dissociation. Science 350:445–450
Pande K, Hutchison CDM, Groenhof G et al (2016) Femtosecond structural dynamics drives the trans/cis isomerization in photoactive yellow protein. Science 352:725–729
Schmidt M (2013) Mix and inject: reaction initiation by diffusion for time-resolved macromolecular crystallography. Adv Cond Matter Phys 10:167276
Henderson R (1995) The potential and limitations of neutrons, electrons and X-rays for atomic resolution microscopy of unstained biological molecules. Q Rev Biophys 28:171–193
Chapman HN, Caleman C, Timneanu N (2014) Diffraction before destruction. Philos Trans R Soc B369:20130313
Creagh DC, Hubbell JH (2006) X-ray absorption (or attenuation) coefficients. Int Tables Crystallogr C:220–229
Son S-K, Young L, Santra R (2011) Impact of hollow-atom formation on coherent X-ray scattering at high intensity. Phys Rev A83:033402
Caleman C, Ortiz C, Marklund E et al (2009) Radiation damage in biological material: electronic properties and electron impact ionization in urea. Europhys Lett 85:18005, erratum 88: 29901
Barty A, Caleman C, Aquila A et al (2012) Self-terminating diffraction gates femtosecond X-ray nanocrystallography measurements. Nat Photon 6:35–40
Nass K, Foucar L, Barends TRM et al (2015) Indications of radiation damage in ferredoxin microcrystals using high-intensity X-FEL beams. J Synchrotron Radiat 22:225–238
Son S-K, Chapman HN, Santra R (2011) Multiwavelength anomalous diffraction at high X-ray intensity. Phys Rev Lett 107:218102
Son S-K, Chapman HN, Santra R (2013) Determination of multiwavelength anomalous diffraction coefficients at high X-ray intensity. J Phys B46:164015
Galli L, Son S-K, Barends TRM et al (2015) Towards phasing using high X-ray intensity. IUCrJ 2:627–634
Serkez S, Kocharyan V, Saldin E et al (2013) Proposal for a scheme to generate 10 TW-level femtosecond X-ray pulses for imaging single protein molecules at the European XFEL. arXiv.org:1306.0804
Davis KM, Kosheleva I, Henning RW et al (2013) Kinetic modeling of the X-ray-induced damage to a metalloprotein. J Phys Chem B117:9161–9169
Owen RL, Rudino-Pinera E, Garman EF (2006) Experimental determination of the radiation dose limit for cryocooled protein crystals. Proc Natl Acad Sci U S A 103:4912–4917
Garman EF, Weik M (2015) Radiation damage to macromolecules: kill or cure? J Synchrotron Radiat 22:195–200
Cowan A, Nave C (2008) The optimum conditions to collect X-ray data from very small samples. J Synchrotron Radiat 15:458–462
Coquelle N, Brewster AS, Kapp U et al (2015) Raster-scanning serial protein crystallography using micro- and nano-focused synchrotron beams. Acta Crystallogr D Biol Crystallogr 71:1184–1196
Koopmann R, Cupelli K, Redecke L et al (2012) In vivo protein crystallization opens new routes in structural biology. Nat Methods 9:259–262
Redecke L, Nass K, DePonte DP et al (2013) Natively inhibited Trypanosoma brucei cathepsin B structure determined by using an X-ray laser. Science 339:227–230
Jakobi AJ, Passon DM, Knoops K et al (2016) In cellulo serial crystallography of alcohol oxidase crystals inside yeast cells. IUCrJ 3:88–95
Sawaya MR, Cascio D, Gingery M et al (2014) Protein crystal structure obtained at 2.9 Å resolution from injecting bacterial cells into an X-ray free-electron laser beam. Proc Natl Acad Sci U S A 111:12769–12774
Ayyer K, Philipp HT, Tate MW et al (2015) Determination of crystallographic intensities from sparse data. IUCrJ 2:29–34
Wierman JL, Lan T-Y, Tate MW et al (2016) Protein crystal structure from non-oriented, single-axis sparse X-ray data. IUCrJ 3:43–50
Loh NTD, Elser V (2009) Reconstruction algorithm for single-particle diffraction imaging experiments. Phys Rev E80:026705
Fung R, Shneerson V, Saldin DK et al (2009) Structure from fleeting illumination of faint spinning objects in flight. Nat Phys 5:64–67
White TA (2014) Post-refinement method for snapshot serial crystallography. Philos Trans R Soc B369:20130330
Gati C, Oberthuer D, Yefanov O et al (2017) Atomic structure of granulin determined from native nanocrystalline granulovirus using an X-ray free-electron laser. Proc Natl Acad Sci U S A 114:2247–2252
Galli L, Metcalf P, Chapman HN (2015) Implications of the focal beam profile in serial femtosecond crystallography. Proc SPIE 9511:95110H
Liang M, Williams GJ, Messerschmidt M et al (2015) The coherent X-ray imaging instrument at the linac coherent light source. J Synchrotron Radiat 22:514–519
Hart P, Boutet S, Carini G et al (2012) The CSPAD megapixel X-ray camera at LCLS. Proc SPIE 8504:85040C–850411
Kärtner F, Ahr F, Calendron A-L et al (2016) AXSIS: exploring the frontiers in attosecond X-ray science, imaging and spectroscopy. Nucl Instrum Methods Phys Res A829:24–29
Allahgholi A, Becker J, Bianco L et al (2015) AGIPD, a high dynamic range fast detector for the European XFEL. J Instrum 10:C01023
Brehm W, Diederichs K (2014) Breaking the indexing ambiguity in serial crystallography. Acta Crystallogr D Biol Crystallogr 70:101–109
Ginn HM, Messerschmidt M, Ji X et al (2015) Structure of CPV17 polyhedrin determined by the improved analysis of serial femtosecond crystallographic data. Nat Commun 6:6435
Barends TRM, Foucar L, Botha S et al (2014) De novo protein crystal structure determination from X-ray free-electron laser data. Nature 505:244–247
Nakane T, Song C, Suzuki M (2015) Native sulfur/chlorine SAD phasing for serial femtosecond crystallography. Acta Crystallogr D Biol Crystallogr 71:2519–2525
Nass K, Meinhart A, Barends TRM et al (2016) Protein structure determination by single-wavelength anomalous diffraction phasing of X-ray free-electron laser data. IUCrJ 3:180–191
Schmidt S (2014) GrainSpotter: a fast and robust polycrystalline indexing algorithm. J Appl Crystallogr 47:276–284
Gildea RJ, Waterman DG, Parkhurst JM et al (2014) New methods for indexing multi-lattice diffraction data. Acta Crystallogr D Biol Crystallogr 70:2652–2666
Ginn HM, Roedig P, Kuo A et al (2016) TakeTwo: an indexing algorithm suited to still images with known crystal parameters. Acta Crystallogr D Biol Crystallogr 72:956–965
White TA, Barty A, Stellato F et al (2013) Crystallographic data processing for free-electron laser sources. Acta Crystallogr D Biol Crystallogr 69:1231–1240
Hirata K, Shinzawa-Itoh K, Yano N et al (2014) Determination of damage-free crystal structure of an X-ray-sensitive protein using an XFEL. Nat Methods 11:734–736
Cohen AE, Soltis SM, Gonzalez A et al (2014) Goniometer-based femtosecond crystallography with X-ray free electron lasers. Proc Natl Acad Sci U S A 111:17122–17127
Diederichs K, Karplus PA (2013) Better models by discarding data? Acta Crystallogr D Biol Crystallogr 69:1215–1222
Zhang T, Jin S, Gu Y et al (2015) SFX analysis of non-biological polycrystalline samples. IUCrJ 2:322–326
Liu Q, Dahmane T, Zhang Z et al (2012) Structures from anomalous diffraction of native biological macromolecules. Science 336:1033–1037
Schlichting I (2015) Serial femtosecond crystallography: the first five years. IUCrJ 2:246–255
Chavas LMG, Gumprecht L, Chapman HN (2015) Possibilities for serial femtosecond crystallography sample delivery at future light sources. Struct Dyn 2:041709
Chapman HN (2015) Serial femtosecond crystallography. Synchrotron Radiat News 28:20–24
Gruner SM, Lattman EE (2015) Biostructural science inspired by next-generation X-ray sources. Annu Rev Biophys 44:33–51
Boutet S, Williams SG (2010) The coherent X-ray imaging (CXI) instrument at the linac coherent light source (LCLS). New J Phys 12:035024
Bozek JD (2009) AMO instrumentation for the LCLS X-ray FEL. Eur Phys J 169:129–132
Song C, Tono K, Park J et al (2014) Multiple application X-ray imaging chamber for single-shot diffraction experiments with femtosecond X-ray laser pulses. J Appl Crystallogr 47:188–197
Chapman HN, Fromme P, Barty A et al (2011) Femtosecond X-ray protein nanocrystallography. Nature 470:73–77
Gañan Calvo AM (1998) Generation of steady liquid microthreads and micron-sized monodisperse sprays in gas streams. Phys Rev Lett 80:285–288
Awel S, Kirian RA, Eckerskorn N et al (2016) Visualizing aerosol-particle injection for diffractive-imaging experiments. Opt Express 24:6507–6521
Stan CA, Milathianaki D, Laksmono H et al (2016) Liquid explosions induced by X-ray laser pulses. Nat Phys 12:966–971
Roessler CG, Kuczewski A, Stearns R et al (2013) Acoustic methods for high-throughput protein crystal mounting at next-generation macromolecular crystallographic beamlines. J Synchrotron Radiat 20:805–808
Ganan-Calvo AM, Gonzalez-Prieto R, Riesco-Chueca P (2007) Focusing capillary jets close to the continuum limit. Nat Phys 3:737–742
Wang D, Weierstall U, Pollack L et al (2014) Double-focusing mixing jet for XFEL study of chemical kinetics. J Synchrotron Radiat 21:1364–1366
Oberhuer D et al (2017) Room-temperature structure determination of RNA polymerase II enabled by double-flow focusing injection. Sci Rep 7:44628
Lee C-Y, Chang C-L, Wang Y-N et al (2011) Microfluidic mixing: a review. Int J Mol Sci 12:3263
Liu P, Ziemann PJ, Kittleson DB et al (1995) Generating particle beams of controlled dimensions and divergence: I. Theory of particle motion in aerodynamic lenses and nozzle expansions. Aerosol Sci Technol 22:314–324
Seibert MM, Ekeberg T, Maia FRNC et al (2011) Single mimivirus particles intercepted and imaged with an X-ray laser. Nature 470:78–81
Aquila A, Barty A, Bostedt C et al (2015) The linac coherent light source single particle imaging road map. Struct Dyn 2:041701
Eckerskorn N, Bowman R, Kirian RA et al (2015) Optically induced forces imposed in an optical funnel on a stream of particles in air or vacuum. Phys Rev Appl 4:064001
Sherrell DA, Foster AJ, Hudson L et al (2015) A modular and compact portable mini-endstation for high-precision, high-speed fixed target serial crystallography at FEL and synchrotron sources. J Synchrotron Radiat 22:1372–1378
Yuk JM, Park J, Ercius P et al (2012) High-resolution EM of colloidal nanocrystal growth using graphene liquid cells. Science 336:61–64
Spence JCH, Kirian RA, Wang X et al (2011) Phasing of coherent femtosecond X-ray diffraction from size- varying nanocrystals. Opt Express 19:2866–2873
Kirian RA, Bean RJ, Beyerlein KR et al (2015) Direct phasing of finite crystals illuminated with a free-electron laser. Phys Rev X 5:011015
Ayyer K, Yefanov OM, Oberthür D (2016) Macromolecular diffractive imaging using imperfect crystals. Nature 530:202–206
Millane RP (1990) Phase retrieval in crystallography and optics. J Opt Soc Am A 7:394–411
Sayre D, Chapman HN (1995) X-ray microscopy. Acta Crystallogr A 51:237–252
Sayre D (1952) Some implications of a theorem due to Shannon. Acta Crystallogr 5:843
Oszlányi G, Süto A (2008) The charge flipping algorithm. Acta Crystallogr A 64:123–134
Elser V, Millane RP (2008) Reconstruction of an object from its symmetry-averaged diffraction pattern. Acta Crystallogr A 64:273–279
Thibault P, Elser V (2010) X-ray diffraction microscopy. Annu Rev Cond Matter Phys 1:237–255
Fienup JR (1982) Phase retrieval algorithms: a comparison. Appl Opt 21:2758–2769
Bragg L, Perutz MF (1952) The structure of Haemoglobin. Proc R Soc Lond 213:425–435
He H, Su W-P (2015) Direct phasing of protein crystals with high solvent content. Acta Crystallogr A 71:92–98
Wall ME, Adams PD, Fraser JS et al (2014) Diffuse X-ray scattering to model protein motions. Structure 22:182–184
Crowther R, DeRosier D, Klug A (1970) The reconstruction of a three-dimensional structure from its projections and its applications to electron microscopy. Proc R Soc Lond 317:319–340
Roedig P, Duman R, Sanchez-Weatherby J et al (2016) Room-temperature macromolecular crystallography using a micro-patterned silicon chip with minimal background scattering. J Appl Crystallogr 49:968–975
Stellato F, Oberthür D, Liang M et al (2014) Room-temperature macromolecular serial crystallography using synchrotron radiation. IUCrJ 1:204–212
Nogly P, James D, Wang D et al (2015) Lipidic cubic phase serial millisecond crystallography using synchrotron radiation. IUCrJ 2:168–176
Botha S, Nass K, Barends TRM et al (2015) 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
Boutet S, Lomb L, Williams GJ et al (2012) High-resolution protein structure determination by serial femtosecond crystallography. Science 337:362–364
Gati C, Bourenkov G, Klinge M et al (2014) Serial crystallography on in vivo grown microcrystals using synchrotron radiation. IUCrJ 1:87–94
Kupitz C, Basu S, Grotjohann I et al (2014) Serial time-resolved crystallography of photosystem II using a femtosecond X-ray laser. Nature 513:261–265
Pedrini B, Tsai C-J, Capitani G et al (2014) 7 Ã… resolution in protein two-dimensional-crystal X-ray diffraction at linac coherent light source. Philos Trans R Soc Lond B Biol Sci B369:20130500
Holton JM (2009) A beginner’s guide to radiation damage. J Synchrotron Radiat 16:133–142
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer Science+Business Media LLC
About this protocol
Cite this protocol
Chapman, H.N. (2017). Structure Determination Using X-Ray Free-Electron Laser Pulses. In: Wlodawer, A., Dauter, Z., Jaskolski, M. (eds) Protein Crystallography. Methods in Molecular Biology, vol 1607. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7000-1_12
Download citation
DOI: https://doi.org/10.1007/978-1-4939-7000-1_12
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-6998-2
Online ISBN: 978-1-4939-7000-1
eBook Packages: Springer Protocols