Advertisement

Time-Resolved Macromolecular Crystallography at Modern X-Ray Sources

  • Marius Schmidt
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1607)

Abstract

Time-resolved macromolecular crystallography unifies protein structure determination with chemical kinetics. With the advent of fourth generation X-ray sources the time-resolution can be on the order of 10–40 fs, which opens the ultrafast time scale to structure determination. Fundamental motions and transitions associated with chemical reactions in proteins can now be observed. Moreover, new experimental approaches at synchrotrons allow for the straightforward investigation of all kind of reactions in biological macromolecules. Here, recent developments in the field are reviewed.

Key words

Time-resolved macromolecular crystallography Time-resolved serial femtosecond crystallography Structure based enzymology Chemical kinetics 

Notes

Acknowledgment

M.S. thanks Vukica Šrajer for reading, and commenting on, an earlier version of the manuscript. This work is supported by the BioXFEL Science and Technology Center (NSF grant 1231306).

References

  1. 1.
    Bourgeois D, Weik M (2009) Kinetic protein crystallography: a tool to watch proteins in action. Crystallogr Rev 15:87–118CrossRefGoogle Scholar
  2. 2.
    Weik M, Colletier JP (2010) Temperature-dependent macromolecular X-ray crystallography. Acta Crystallogr D Biol Crystallogr 66:437–446CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Nienhaus K, Ostermann A, Nienhaus GU et al (2005) Ligand migration and protein fluctuations in myoglobin mutant L29W. Biochemistry 44:5095–5105CrossRefPubMedGoogle Scholar
  4. 4.
    Moffat K (1989) Time-resolved macromolecular crystallography. Annu Rev Biophys Biophys Chem 18:309–332CrossRefPubMedGoogle Scholar
  5. 5.
    Moffat K, Szebenyi D, Bilderback D (1984) X-ray Laue diffraction from protein crystals. Science 223:1423–1425CrossRefPubMedGoogle Scholar
  6. 6.
    Barker AI, Southworth-Davies RJ, Paithankar KS et al (2009) Room-temperature scavengers for macromolecular crystallography: increased lifetimes and modified dose dependence of the intensity decay. J Synchrotron Radiat 16:205–216CrossRefPubMedGoogle Scholar
  7. 7.
    Youngblut M, Judd ET, Srajer V et al (2012) Laue crystal structure of Shewanella oneidensis cytochrome c nitrite reductase from a high-yield expression system. J Biol Inorg Chem 17:647–662CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Schmidt M, Srajer V, Purwar N et al (2012) The kinetic dose limit in room-temperature time-resolved macromolecular crystallography. J Synchrotron Radiat 19:264–273CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Schmidt M (2015) Time-resolved crystallography at X-ray free electron lasers and synchrotron light sources. Synchrotron Radiat News 28:25–30CrossRefGoogle Scholar
  10. 10.
    Schmidt M (2008) Structure based enzyme kinetics by time-resolved X-ray crystallography. In: Zinth W, Braun M, Gilch P (eds) Ultrashort laser pulses in medicine and biology, Biological and medical physics, biomedical engineering. Springer, BerlinGoogle Scholar
  11. 11.
    Ren Z, Bourgeois D, Helliwell JR et al (1999) Laue crystallography: coming of age. J Synchrotron Radiat 6:891–917CrossRefGoogle Scholar
  12. 12.
    Stoddard BL (1998) New results using Laue diffraction and time-resolved crystallography. Curr Opin Struct Biol 8:612–618CrossRefPubMedGoogle Scholar
  13. 13.
    Srajer V (2013) Time-resolved macromolecular crystallography in practice at BioCARS, advanced photon source: from data collection to structures of intermediates. In: Howard JAK, Sparkes HA, Raithby PR, Churakov AV (eds) The future of dynamic structural science. Springer, New York, pp 237–251Google Scholar
  14. 14.
    Schmidt M, Ihee H, Pahl R et al (2005) Protein-ligand interaction probed by time-resolved crystallography. Methods Mol Biol 305:115–154PubMedGoogle Scholar
  15. 15.
    Bourgeois D, Royant A (2005) Advances in kinetic protein crystallography. Curr Opin Struct Biol 15:538–547CrossRefPubMedGoogle Scholar
  16. 16.
    Barends TR, Foucar L, Ardevol A et al (2015) Direct observation of ultrafast collective motions in CO myoglobin upon ligand dissociation. Science 350:445–450CrossRefPubMedGoogle Scholar
  17. 17.
    Bionta MR, Lemke HT, Cryan JP et al (2011) Spectral encoding of X-ray/optical relative delay. Opt Express 19:21855–21865CrossRefPubMedGoogle Scholar
  18. 18.
    Hartmann N, Helml W, Galler A et al (2014) Sub-femtosecond precision measurement of relative X-ray arrival time for free-electron lasers. Nat Photonics 8:706–709CrossRefGoogle Scholar
  19. 19.
    Pande K, Hutchison CDM, Groenhof G et al (2016) Femtosecond structural dynamics drives the trans/cis isomerization in photoactive yellow protein. Science 352:725–729CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Auldridge ME, Forest KT (2011) Bacterial phytochromes: more than meets the light. Crit Rev Biochem Mol Biol 46:67–88CrossRefPubMedGoogle Scholar
  21. 21.
    Schmidt M, Patel A, Zhao Y et al (2007) Structural basis for the photochemistry of alpha-phycoerythrocyanin. Biochemistry 46:416–423CrossRefPubMedGoogle Scholar
  22. 22.
    Purwar N, Tenboer J, Tripathi S et al (2013) Spectroscopic studies of model photo-receptors: validation of a nanosecond time-resolved micro-spectrophotometer design using photoactive yellow protein and α-phycoerythrocyanin. Int J Mol Sci 14:18881–18898CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Moglich A, Ayers RA, Moffat K (2010) Addition at the molecular level: signal integration in designed Per-ARNT-Sim receptor proteins. J Mol Biol 400:477–486CrossRefPubMedGoogle Scholar
  24. 24.
    Moffat K (2014) Time-resolved crystallography and protein design: signalling photoreceptors and optogenetics. Phil Trans R Soc London B369:20130568CrossRefGoogle Scholar
  25. 25.
    Schlichting I, Almo SC, Rapp G et al (1990) Time-resolved X-ray crystallographic study of the conformational change in Ha-Ras p21 protein on GTP hydrolysis. Nature 345:309–315CrossRefPubMedGoogle Scholar
  26. 26.
    Adams SR, Tsien RY (1993) Controlling cell chemistry with caged compounds. Annu Rev Physiol 55:755–784CrossRefPubMedGoogle Scholar
  27. 27.
    Goelder M, Givens R (eds) (2005) Dynamic studies in biology: phototriggers, photoswitches and caged biomolecules. Wiley-VCH, WeinheimGoogle Scholar
  28. 28.
    Ursby T, Weik M, Fioravanti E et al (2002) Cryophotolysis of caged compounds: a technique for trapping intermediate states in protein crystals. Acta Crystallogr D Biol Crystallogr 58:607–614CrossRefPubMedGoogle Scholar
  29. 29.
    Bourgeois D, Weik M (2005) New perspectives in kinetic protein crystallography using caged compounds. In: Dynamic studies in biology: phototriggers, photoswitches and caged biomolecules. Wiley-VCH, Weinheim, pp 410–432Google Scholar
  30. 30.
    Kurisu G, Sugimoto A, Kai Y et al (1997) A flow cell suitable for time-resolved X-ray crystallography by the Laue method. J Appl Crystallogr 30:555–556CrossRefGoogle Scholar
  31. 31.
    Moffat K, Chen Y, Ng KM et al (1992) Time-resolved crystallography—principles, problems and practice. Philos Trans R Soc A340:175–189CrossRefGoogle Scholar
  32. 32.
    Srajer V, Teng TY, Ursby T et al (1996) Photolysis of the carbon monoxide complex of myoglobin: nanosecond time-resolved crystallography. Science 274:1726–1729CrossRefPubMedGoogle Scholar
  33. 33.
    Ren Z, Perman B, Srajer V et al (2001) A molecular movie at 1.8 a resolution displays the photocycle of photoactive yellow protein, a eubacterial blue-light receptor, from nanoseconds to seconds. Biochemistry 40:13788–13801CrossRefPubMedGoogle Scholar
  34. 34.
    Srajer V, Ren Z, Teng TY et al (2001) Protein conformational relaxation and ligand migration in myoglobin: a nanosecond to millisecond molecular movie from time-resolved Laue X-ray diffraction. Biochemistry 40:13802–13815CrossRefPubMedGoogle Scholar
  35. 35.
    Srajer V, Crosson S, Schmidt M et al (2000) Extraction of accurate structure-factor amplitudes from Laue data: wavelength normalization with wiggler and undulator X-ray sources. J Synchrotron Radiat 7:236–244CrossRefPubMedGoogle Scholar
  36. 36.
    Graber T, Anderson S, Brewer H et al (2011) BioCARS: a synchrotron resource for time-resolved X-ray science. J Synchrotron Radiat 18:658–670CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Ihee H, Rajagopal S, Srajer V et al (2005) Visualizing reaction pathways in photoactive yellow protein from nanoseconds to seconds. Proc Natl Acad Sci U S A 102:7145–7150CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Schmidt M, Srajer V, Henning R et al (2013) Protein energy landscapes determined by five-dimensional crystallography. Acta Crystallogr D Biol Crystallogr 69:2534–2542CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Jung YO, Lee JH, Kim J et al (2013) Volume-conserving trans-cis isomerization pathways in photoactive yellow protein visualized by picosecond X-ray crystallography. Nat Chem 5:212–220CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Schotte F, Cho HS, Kaila VR et al (2012) Watching a signaling protein function in real time via 100-ps time-resolved Laue crystallography. Proc Natl Acad Sci U S A 109:19256–19261CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Ren Z, Moffat K (1995) Quantitative analysis of synchrotron Laue diffraction patterns in macromolecular crystallography. J Appl Crystallogr 28:461–481CrossRefGoogle Scholar
  42. 42.
    Schmidt M, Rajagopal S, Ren Z et al (2003) Application of singular value decomposition to the analysis of time-resolved macromolecular X-ray data. Biophys J 84:2112–2129CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Henry ER, Hofrichter J (1992) Singular value decomposition—application to analysis of experimental data. Meth Enzymol 210:129–192CrossRefGoogle Scholar
  44. 44.
    Terwilliger TC, Berendzen J (1996) Bayesian difference refinement. Acta Crystallogr D Biol Crystallogr 52:1004–1011CrossRefPubMedGoogle Scholar
  45. 45.
    Tripathi S, Srajer V, Purwar N et al (2012) pH dependence of the photoactive yellow protein photocycle investigated by time-resolved crystallography. Biophys J 102:325–332CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Emsley P, Lohkamp B, Scott WG et al (2010) Features and development of coot. Acta Crystallogr D Biol Crystallogr 66:486–501CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Murshudov GN, Skubak P, Lebedev AA et al (2011) REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr D Biol Crystallogr 67:355–367CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Schmidt M, Graber T, Henning R et al (2010) Five-dimensional crystallography. Acta Crystallogr A 66:198–206CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Holton JM, Frankel KA (2010) The minimum crystal size needed for a complete diffraction data set. Acta Crystallogr D Biol Crystallogr 66:393–408CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Lomb L, Barends TR, Kassemeyer S et al (2011) Radiation damage in protein serial femtosecond crystallography using an X-ray free-electron laser. Phys Rev B84:214111CrossRefGoogle Scholar
  51. 51.
    Chapman HN, Barty A, Bogan MJ et al (2006) Femtosecond diffractive imaging with a soft-X-ray free-electron laser. Nat Phys 2:839–843CrossRefGoogle Scholar
  52. 52.
    Neutze R, Wouts R, van der Spoel D et al (2000) Potential for biomolecular imaging with femtosecond X-ray pulses. Nature 406:752–757CrossRefPubMedGoogle Scholar
  53. 53.
    Chapman HN, Fromme P, Barty A et al (2011) Femtosecond X-ray protein nanocrystallography. Nature 470:73–77CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Boutet S, Lomb L, Williams GJ et al (2012) High-resolution protein structure determination by serial femtosecond crystallography. Science 337:362–364CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Weierstall U, Spence JC, Doak RB (2012) Injector for scattering measurements on fully solvated biospecies. Rev Sci Instrum 83:035108CrossRefPubMedGoogle Scholar
  56. 56.
    Weierstall U, James D, Wang C et al (2014) Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography. Nat Commun 5:3309CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Conrad C, Basu S, James D et al (2015) A novel inert crystal delivery medium for serial femtosecond crystallography. IUCrJ 2:421–430CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Sugahara M, Mizohata E, Nango E et al (2015) Grease matrix as a versatile carrier of proteins for serial crystallography. Nat Methods 12:61–63CrossRefPubMedGoogle Scholar
  59. 59.
    Sierra RG, Laksmono H, Kern J et al (2012) Nanoflow electrospinning serial femtosecond crystallography. Acta Crystallogr D Biol Crystallogr 68:1584–1587CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Mueller C, Marx A, Epp SW et al (2015) Fixed target matrix for femtosecond time-resolved and in situ serial micro-crystallography. Struct Dyn 2:054302CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Hunter MS, Segelke B, Messerschmidt M et al (2014) Fixed-target protein serial microcrystallography with an X-ray free electron laser. Sci Rep 4:6026CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Zarrine-Afsar A, Barends TRM, Muller C et al (2012) Crystallography on a chip. Acta Crystallogr D Biol Crystallogr 68:321–323CrossRefPubMedGoogle Scholar
  63. 63.
    Roessler CG, Agarwal R, Allaire M et al (2016) Acoustic injectors for drop-on-demand serial femtosecond crystallography. Structure 24:631–640CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Kirian RA, White TA, Holton JM et al (2011) Structure-factor analysis of femtosecond microdiffraction patterns from protein nanocrystals. Acta Crystallogr A 67:131–140CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    White TA, Kirian RA, Martin AV et al (2012) CrystFEL: a software suite for snapshot serial crystallography. J Appl Crystallogr 45:335–341CrossRefGoogle Scholar
  66. 66.
    Tenboer J, Basu S, Zatsepin N et al (2014) Time-resolved serial crystallography captures high-resolution intermediates of photoactive yellow protein. Science 346:1242–1246CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Aquila A, Hunter MS, Doak RB et al (2012) Time-resolved protein nanocrystallography using an X-ray free-electron laser. Opt Express 20:2706–2716CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Kupitz C, Basu S, Grotjohann I et al (2014) Serial time-resolved crystallography of photosystem II using a femtosecond X-ray laser. Nature 513:5CrossRefGoogle Scholar
  69. 69.
    Lincoln CN, Fitzpatrick AE, van Thor JJ (2012) Photoisomerisation quantum yield and non-linear cross-sections with femtosecond excitation of the photoactive yellow protein. Phys Chem Chem Phys 14:15752–15764CrossRefPubMedGoogle Scholar
  70. 70.
    Nakamura R, Hamada N, Ichida H et al (2007) Coherent oscillations in ultrafast fluorescence of photoactive yellow protein. J Chem Phys 127:215102CrossRefPubMedGoogle Scholar
  71. 71.
    Creelman M, Kumauchi M, Hoff WD et al (2014) Chromophore dynamics in the PYP photocycle from femtosecond stimulated Raman spectroscopy. J Phys Chem B118:659–667CrossRefGoogle Scholar
  72. 72.
    Hutchison CDM, Tenboer J, Kupitz C et al (2016) Photocycle populations with femtosecond excitation of crystalline photoactive yellow protein. J Chem Phys Lett 654:63–71CrossRefGoogle Scholar
  73. 73.
    Liang M, Williams GJ, Messerschmidt M et al (2015) The coherent X-ray imaging instrument at the Linac coherent light source. J Synchrotron Radiat 22:514–519CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Groenhof G, Bouxin-Cademartory M, Hess B et al (2004) Photoactivation of the photoactive yellow protein: why photon absorption triggers a trans-to-cis isomerization of the chromophore in the protein. J Am Chem Soc 126:4228–4233CrossRefPubMedGoogle Scholar
  75. 75.
    Groenhof G (2013) Introduction to QM/MM simulations. Methods Mol Biol 924:43–66CrossRefPubMedGoogle Scholar
  76. 76.
    Polli D, Altoe P, Weingart O et al (2010) Conical intersection dynamics of the primary photoisomerization event in vision. Nature 467:440–443CrossRefPubMedGoogle Scholar
  77. 77.
    Johnson PJ, Halpin A, Morizumi T et al (2015) Local vibrational coherences drive the primary photochemistry of vision. Nat Chem 7:980–986CrossRefPubMedGoogle Scholar
  78. 78.
    Blancafort L (2014) Photochemistry and photophysics at extended seams of conical intersection. Chemphyschem 15:3166–3181CrossRefPubMedGoogle Scholar
  79. 79.
    Schmidt M (2013) Mix and inject, reaction initiation by diffusion for time-resolved macromolecular crystallography. Adv Condens Mat Phys 2013:1–10CrossRefGoogle Scholar
  80. 80.
    Botha S, Nass K, Barends TR 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 71:387–397CrossRefPubMedGoogle Scholar
  81. 81.
    Stellato F, Oberthuer D, Mengning L et al (2014) Room-temperature macromolecular serial crystallography using synchrotron radiation. IUCrJ 1:204–212CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Pawate AS, Srajer V, Schieferstein J et al (2015) Towards time-resolved serial crystallography in a microfluidic device. Acta Crystallogr F Struct Biol Commun 71:823–830CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Perry SL, Guha S, Pawate AS et al (2014) Serial Laue diffraction on a microfluidic crystallization device. J Appl Crystallogr 47:1975–1982CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Nogly P, James D, Wang D et al (2015) Lipidic cubic phase serial millisecond crystallography using synchrotron radiation. IUCrJ 2:168–176CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  1. 1.Kenwood Interdisciplinary Research Complex, Physics DepartmentUniversity of Wisconsin-MilwaukeeMilwaukeeUSA

Personalised recommendations