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Other Structure Determination Methods

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Part of the Computational Biology book series (COBO, volume 25)

Abstract

There are more ways of gaining insight into macromolecular structure than X-ray diffraction. Like X-ray diffraction, some of these are based on the generation of ordered arrays of the molecule to be studied. For many reasons, based on either the protein or its function, this is not always possible. Others, some of which are currently enjoying a marked increase in popularity, do not require crystals. Many of these come with the added advantage that they can be used to capture reaction intermediates and/or enable the experimenter to observe changes in specific amino acids, which is often not possible with X-ray diffraction methods. This chapter divides into two sections; those methods that can be used to obtain a 3D structure (neutron diffraction, cryogenic electron microscopy, nuclear magnetic resonance, and X-ray free electron laser diffraction) and those that are suitable for more general structural information (chemical cross linking, fluorescence resonance energy transfer, circular dichroism). Virtually all of the methods discussed below can be expanded for the study of other aspects of macromolecular structure-function relationships, and some, such as fluorescence and chemical cross linking, are a subset of a rich methodology for the study of macromolecules.

References

  1. 1.
    Adrian, M., Dubochet, J., Lepault, J., & McDowall, A. W. (1984). Cryo-electron microscopy of viruses. Nature, 308(5954), 32–36.CrossRefGoogle Scholar
  2. 2.
    Afonine, P. V., Mustyakimov, M., Grosse-Kunstleve, R. W., Moriarty, N. W., Langan, P., & Adams, P. D. (2010). Joint X-ray and neutron refinement with phenix.refine. Acta Crystallographica Section D: Biological Crystallography, 66(11), 1153–1163.CrossRefGoogle Scholar
  3. 3.
    Blakeley, M. P., Hasnain, S. S., & Antonyuk, S. V. (2015). Sub-atomic resolution X-ray crystallography and neutron crystallography: promise, challenges and potential. IUCrJ, 2(4), 464–474.CrossRefGoogle Scholar
  4. 4.
    Blakeley, M. P., Langan, P., Niimura, N., & Podjarny, A. (2008). Neutron crystallography: opportunities, challenges, and limitations. Current Opinion in Structural Biology, 18(5), 593–600.CrossRefGoogle Scholar
  5. 5.
    Boivin, S., Kozak, S., & Meijers, R. (2013). Optimization of protein purification and characterization using Thermofluor screens. Protein Expression and Purification, 91(2), 192–206.CrossRefGoogle Scholar
  6. 6.
    Calvey, G. D., Katz, A. M., Schaffer, C. B., & Pollack, L. (2016). Mixing injector enables time-resolved crystallography with high hit rate at X-ray free electron lasers. Structural Dynamics, 3(5), 054301.CrossRefGoogle Scholar
  7. 7.
    Chapman, H. N., Fromme, P., Barty, A., White, T. A., Kirian, R. A., Aquila, A., et al. (2011). Femtosecond X-ray protein nanocrystallography. Nature, 470(7332), 73–77.CrossRefGoogle Scholar
  8. 8.
    Dupeux, F., Rwer, M., Seroul, G., Blot, D., & Mrquez, J. A. (2011). A thermal stability assay can help to estimate the crystallization likelihood of biological samples. Acta Crystallographica Section D: Biological Crystallography, 67(11), 915–919.CrossRefGoogle Scholar
  9. 9.
    Elmlund, D., Le, S. N., & Elmlund, H. (2017). High-resolution cryo-EM: the nuts and bolts. Current Opinion in Structural Biology, 46, 1–6.CrossRefGoogle Scholar
  10. 10.
    Fromme, P., & Spence, J. C. (2011). Femtosecond nanocrystallography using X-ray lasers for membrane protein structure determination. Current Opinion in Structural Biology, 21(4), 509–516.CrossRefGoogle Scholar
  11. 11.
    Gottarelli, G., Lena, S., Masiero, S., Pieraccini, S., & Spada, G. P. (2008). The use of circular dichroism spectroscopy for studying the chiral molecular self-assembly: an overview. Chirality, 20(3–4), 471–485.CrossRefGoogle Scholar
  12. 12.
    Gruene, T., Hahn, H. W., Luebben, A. V., Meilleur, F., & Sheldrick, G. M. (2014). Refinement of macromolecular structures against neutron data with SHELXL2013. Journal of Applied Crystallography, 47(1), 462–466.CrossRefGoogle Scholar
  13. 13.
    Hermanson, G. T. (2013). Bioconjugate techniques (3rd ed.): Academic Press.Google Scholar
  14. 14.
    Jain, R., & Techert, S. (2016). Time-resolved and in-situ X-ray scattering methods beyond photoactivation: utilizing high-flux X-ray sources for the study of ubiquitous non-photoactive proteins. Protein and Peptide Letters, 23(3), 242–254.CrossRefGoogle Scholar
  15. 15.
    Johansson, L. C., Stauch, B., Ishchenko, A., and Cherezov, V. (2017). A bright future for serial femtosecond crystallography with XFELs. Trends in Biochemical Sciences.Google Scholar
  16. 16.
    Joni, S. (2016). Cryo-electron microscopy analysis of structurally heterogeneous macromolecular complexes. Computational and Structural Biotechnology Journal, 14, 385–390.CrossRefGoogle Scholar
  17. 17.
    Kurgan, L., Razib, A. A., Aghakhani, S., Dick, S., Mizianty, M., & Jahandideh, S. (2009). CRYSTALP2: sequence-based protein crystallization propensity prediction. BMC Structural Biology, 9, 50.CrossRefGoogle Scholar
  18. 18.
    Kwan, A. H., Mobli, M., Gooley, P. R., King, G. F., & Mackay, J. P. (2011). Macromolecular NMR spectroscopy for the non-spectroscopist. FEBS Journal, 278(5), 687–703.CrossRefGoogle Scholar
  19. 19.
    Lakowicz, J. R. (2006). In J. R. Lakowicz (Ed.), Principles of fluorescence spectroscopy (3rd ed.). US: Springer.Google Scholar
  20. 20.
    Martin-Garcia, J. M., Conrad, C. E., Coe, J., Roy-Chowdhury, S., & Fromme, P. (2016). Serial femtosecond crystallography: a revolution in structural biology. Archives of Biochemistry and Biophysics, 602, 32–47.CrossRefGoogle Scholar
  21. 21.
    Meierhenrich, U. J., Filippi, J.-J., Meinert, C., Bredehft, J. H., Takahashi, J.-I., Nahon, L., et al. (2010). Circular dichroism of amino acids in the vacuum-ultraviolet region. Angewandte Chemie International Edition, 49(42), 7799–7802.CrossRefGoogle Scholar
  22. 22.
    Micsonai, A., Wien, F., Kernya, L., Lee, Y.-H., Goto, Y., Rfrgiers, M., et al. (2015). Accurate secondary structure prediction and fold recognition for circular dichroism spectroscopy. Proceedings of the National Academy of Sciences, 112(24), E3095–E3103.CrossRefGoogle Scholar
  23. 23.
    Milazzo, A.-C., Leblanc, P., Duttweiler, F., Jin, L., Bouwer, J. C., Peltier, S., et al. (2005). Active pixel sensor array as a detector for electron microscopy. Ultramicroscopy, 104(2), 152–159.CrossRefGoogle Scholar
  24. 24.
    O’Dell, W. B., Bodenheimer, A. M., & Meilleur, F. (2016). Neutron protein crystallography: a complementary tool for locating hydrogens in proteins. Archives of Biochemistry and Biophysics, 602, 48–60.CrossRefGoogle Scholar
  25. 25.
    Opella, S. J., & Marassi, F. M. (2017). Applications of NMR to membrane proteins. Archives of Biochemistry and Biophysics, 628, 92–101.CrossRefGoogle Scholar
  26. 26.
    Park, S.-H., & Raines, R. T. (2004). Fluorescence gel retardation assay to detect Protein-Protein Interactions. In Protein-Protein Interactions, Methods in molecular biology (pp. 155–159): Humana Press. https://doi.org/10.1385/1-59259-762-9:155.
  27. 27.
    Ranjbar, B., & Gill, P. (2009). Circular dichroism techniques: biomolecular and nanostructural analyses- a review. Chemical Biology & Drug Design, 74(2), 101–120.CrossRefGoogle Scholar
  28. 28.
    Slabinski, L., Jaroszewski, L., Rychlewski, L., Wilson, I. A., Lesley, S. A., & Godzik, A. (2007). XtalPred: a web server for prediction of protein crystallizability. Bioinformatics, 23(24), 3403–3405.CrossRefGoogle Scholar
  29. 29.
    Snm, M. M., & Kurgan, L. A. (2012). CRYSpred: accurate sequence-based protein crystallization propensity prediction using sequence-derived structural characteristics. Protein and Peptide Letters, 19(1), 40–49.CrossRefGoogle Scholar
  30. 30.
    Takizawa, Y., Binshtein, E., Erwin, A. L., Pyburn, T. M., Mittendorf, K. F., & Ohi, M. D. (2017). While the revolution will not be crystallized, biochemistry reigns supreme. Protein Science, 26(1), 69–81.CrossRefGoogle Scholar
  31. 31.
    Johnson, W. C, Jr. (1988). Secondary structure of proteins through circular dichroism spectroscopy. Annual Review of Biophysics and Biophysical Chemistry, 17(1), 145–166.CrossRefGoogle Scholar
  32. 32.
    Ziarek, J. J., Baptista, D., & Wagner, G. (2017). Recent developments in solution nuclear magnetic resonance (NMR)-based molecular biology. Journal of Molecular Medicine, 1–8.Google Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.iXpressGenes, Inc.HuntsvilleUSA
  2. 2.University of Alabama in HuntsvilleHuntsvilleUSA

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