Conformational Motions of Disordered Proteins

Chapter

Abstract

Molecular dynamics in proteins animate and play a vital role for biologically relevant processes of these biomacromolecules. Quasielastic incoherent neutron scattering (QENS) is a well-suited experimental method to study protein dynamics from the picosecond to several nanoseconds and in the Ångström length-scale. In QENS experiments of protein solutions hydrogens act as reporters for the motions of methyl groups or amino acids to which they are bound. Neutron Spin-Echo spectroscopy (NSE) on the other hand offers the highest energy resolution in the field of neutron spectroscopy. It enables the study of slow collective motions in proteins up to several hundred nanoseconds and in the nanometre length-scale. In the following chapter I will present recent experimental studies that demonstrate the relevance of molecular dynamics for protein folding and for conformational transitions of intrinsically disordered proteins (IDPs). During the folding collapse the protein chain is exploring the accessible conformational space via molecular motions. A large flexibility of partially folded and unfolded proteins, therefore, is mandatory for rapid protein folding. IDPs on the other hand are a special case as they are largely unstructured under physiological conditions in their native states. A large flexibility of IDPs is a characteristic property of the proteins as it allows, for example, the interaction with various binding partners or the rapid response to different conditions.

Notes

Acknowledgements

I would like to thank the Heinz Maier-Leibnitz Zentrum, the Institut Laue-Langevin, the ISIS Pulsed Neutron and Muon Source and the European Synchrotron Radiation Facility for provision of neutron and synchrotron radiation beam time. I also would like to thank my collaborators who appear as co-authors of the presented scientific articles.

References

  1. 1.
    Ball, P. (2008). Water as an active constituent in cell biology. Chemical Reviews, 108, 74–108.  https://doi.org/10.1021/cr068037a.CrossRefGoogle Scholar
  2. 2.
    Banchio, A. J., & Nägele, G. (2008). Short-time transport properties in dense suspensions: From neutral to charge-stabilized colloidal spheres. The Journal of Chemical Physics, 128, 104903.  https://doi.org/10.1063/1.2868773.CrossRefGoogle Scholar
  3. 3.
    Bernadó, P., Mylonas, E., Petoukhov, M. V., et al. (2007). Structural characterization of flexible proteins using small-angle X-ray scattering. Journal of the American Chemical Society, 129, 5656–5664.CrossRefGoogle Scholar
  4. 4.
    Biehl, R., & Richter, D. (2014). Slow internal protein dynamics in solution. Journal of Physics: Condensed Matter, 26, 503103.  https://doi.org/10.1088/0953-8984/26/50/503103.CrossRefGoogle Scholar
  5. 5.
    Cordeiro, T. N., Herranz-Trillo, F., Urbanek, A., et al. (2017). Small-angle scattering studies of intrinsically disordered proteins and their complexes. Current Opinion in Structural Biology, 42, 15–23.CrossRefGoogle Scholar
  6. 6.
    Dunker, A. K., Oldfield, C. J., Meng, J., et al. (2008). The unfoldomics decade: An update on intrinsically disordered proteins. BMC Genomics, 9, S1.  https://doi.org/10.1186/1471-2164-9-S2-S1.CrossRefGoogle Scholar
  7. 7.
    Dyson, H. J., & Wright, P. E. (2017). How does your protein fold? Elucidating the apomyoglobin folding pathway. Accounts of Chemical Research, 50, 105–111.  https://doi.org/10.1021/acs.accounts.6b00511.CrossRefGoogle Scholar
  8. 8.
    Dyson, H. J., & Wright, P. E. (2005). Intrinsically unstructured proteins and their functions. Nature Reviews Molecular Cell Biology, 6, 197–208.CrossRefGoogle Scholar
  9. 9.
    Eliezer, D., & Wright, P. E. (1996). Is apomyoglobin a molten globule? Structural characterization by NMR. Journal of Molecular Biology, 263, 531–538.  https://doi.org/10.1006/jmbi.1996.0596.CrossRefGoogle Scholar
  10. 10.
    Endres, S., Granzin, J., Circolone, F., et al. (2015). Structure and function of a short LOV protein from the marine phototrophic bacterium Dinoroseobacter shibae. BMC Microbiology, 15, 30.  https://doi.org/10.1186/s12866-015-0365-0.CrossRefGoogle Scholar
  11. 11.
    Fitter, J., Gutberlet, T., & Katsaras, J. (Eds.). (2006). Neutron scattering in biology—Techniques and applications. Berlin: Springer.Google Scholar
  12. 12.
    Frauenfelder, H., McMahon, B. H., & Fenimore, P. W. (2003). Myoglobin: The hydrogen atom of biology and a paradigm of complexity. Proceedings of the National Academy of Sciences, 100, 8615–8617.  https://doi.org/10.1073/pnas.1633688100.CrossRefGoogle Scholar
  13. 13.
    Granzin, J., Stadler, A., Cousin, A., et al. (2015). Structural evidence for the role of polar core residue Arg175 in arrestin activation. Scientific Reports, 5, 15808.  https://doi.org/10.1038/srep15808.CrossRefGoogle Scholar
  14. 14.
    Grimaldo, M., Roosen-Runge, F., Hennig, M., et al. (2015). Hierarchical molecular dynamics of bovine serum albumin in concentrated aqueous solution below and above thermal denaturation. Physical Chemistry Chemical Physics, 17, 4645–4655.  https://doi.org/10.1039/c4cp04944f.CrossRefGoogle Scholar
  15. 15.
    Grimaldo, M., Roosen-Runge, F., Zhang, F., et al. (2014). Diffusion and dynamics of γ-globulin in crowded aqueous solutions. The Journal of Physical Chemistry B, 118, 7203–7209.  https://doi.org/10.1021/jp504135z.CrossRefGoogle Scholar
  16. 16.
    Guehrs, E., Stadler, A. M., Flewett, S., et al. (2012). Soft X-ray tomoholography. New Journal of Physics, 14, 13022.  https://doi.org/10.1088/1367-2630/14/1/013022.CrossRefGoogle Scholar
  17. 17.
    Harauz, G., Ishiyama, N., Hill, C. M., et al. (2004). Myelin basic protein-diverse conformational states of an intrinsically unstructured protein and its roles in myelin assembly and multiple sclerosis. Micron, 35, 503–542.CrossRefGoogle Scholar
  18. 18.
    Hennig, M., Roosen-Runge, F., Zhang, F., et al. (2012). Dynamics of highly concentrated protein solutions around the denaturing transition. Soft Matter, 8, 1628.  https://doi.org/10.1039/c1sm06609a.CrossRefGoogle Scholar
  19. 19.
    Jamin, M., & Baldwin, R. L. (1998). Two forms of the pH 4 folding intermediate of apomyoglobin. Journal of Molecular Biology, 276, 491–504.  https://doi.org/10.1006/jmbi.1997.1543.CrossRefGoogle Scholar
  20. 20.
    Kaschner, M., Schillinger, O., Fettweiss, T., et al. (2017). A combination of mutational and computational scanning guides the design of an artificial ligand-binding controlled lipase. Scientific Reports, 7, 42592.  https://doi.org/10.1038/srep42592.CrossRefGoogle Scholar
  21. 21.
    Monkenbusch, M., Stadler, A., Biehl, R., et al. (2015). Fast internal dynamics in alcohol dehydrogenase. The Journal of Chemical Physics, 143, 75101.CrossRefGoogle Scholar
  22. 22.
    Receveur, V., Calmettes, P., Smith, J. C., et al. (1997). Picosecond dynamical changes on denaturation of yeast phosphoglycerate kinase revealed by quasielastic neutron scattering. Proteins, 28, 380–387.CrossRefGoogle Scholar
  23. 23.
    Richter, D., Monkenbusch, M., Arbe, A., & Colmenero, J. (2005). Neutron spin echo in polymer systems. Berlin: Springer.CrossRefGoogle Scholar
  24. 24.
    Stadler, A. M., Demmel, F., Ollivier, J., & Seydel, T. (2016). Picosecond to nanosecond dynamics provide a source of conformational entropy for protein folding. Physical Chemistry Chemical Physics, 18, 21527–21538.  https://doi.org/10.1039/C6CP04146A.CrossRefGoogle Scholar
  25. 25.
    Stadler, A. M., Koza, M. M., & Fitter, J. (2015). Determination of conformational entropy of fully and partially folded conformations of holo- and apomyoglobin. The Journal of Physical Chemistry B, 119, 72–82.  https://doi.org/10.1021/jp509732q.CrossRefGoogle Scholar
  26. 26.
    Stadler, A. M., Pellegrini, E., Johnson, M., et al. (2012). Dynamics-stability relationships in Apo- and Holomyoglobin: A combined neutron scattering and molecular dynamics simulations study. Biophysical Journal, 102, 351–359.CrossRefGoogle Scholar
  27. 27.
    Stadler, A. M., Schweins, R., Zaccai, G., & Lindner, P. (2010). Observation of a large-scale superstructure in concentrated hemoglobin solutions by using small angle neutron scattering. The Journal of Physical Chemistry Letters, 1, 1805–1808.  https://doi.org/10.1021/jz100576c.CrossRefGoogle Scholar
  28. 28.
    Stadler, A. M., Stingaciu, L., Radulescu, A., et al. (2014). Internal nanosecond dynamics in the intrinsically disordered myelin basic protein. Journal of the American Chemical Society, 136, 6987–6994.  https://doi.org/10.1021/ja502343b.CrossRefGoogle Scholar
  29. 29.
    Stadler, A. M., van Eijck, L., Demmel, F., & Artmann, G. (2011). Macromolecular dynamics in red blood cells investigated using neutron spectroscopy. Journal of the Royal Society, Interface, 8, 590–600.  https://doi.org/10.1098/rsif.2010.0306.CrossRefGoogle Scholar
  30. 30.
    Tompa, P. (2012). Intrinsically disordered proteins: A 10-year recap. Trends in Biochemical Sciences, 37, 1–8.CrossRefGoogle Scholar
  31. 31.
    Uversky, V. N. (2002). Natively unfolded proteins: A point where biology waits for physics. Protein Science, 11, 739–756.CrossRefGoogle Scholar
  32. 32.
    Uversky, V. N., Gillespie, J. R., & Fink, A. L. (2000). Why are “natively unfolded” proteins unstructured under physiologic conditions? Proteins, 41, 415–427.CrossRefGoogle Scholar
  33. 33.
    Wright, P. E., & Dyson, H. J. (2009). Linking folding and binding. Current Opinion in Structural Biology, 19, 31–38.  https://doi.org/10.1016/j.sbi.2008.12.003.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Jülich Centre for Neutron Science, JCNS and Institute for Complex Systems ICS, Forschungszentrum Jülich GmbHJülichGermany

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