Structural Studies of Proteins and Nucleic Acids in Solution Using Small Angle X-Ray Scattering (SAXS)

  • R. Das
  • S. Doniach
Reference work entry

1 Introduction

Over the last 20 years, the application of small angle x-ray scattering (SAXS) to the structural investigation of biological macromolecules has made tremendous progress. Historically used to measure molecule size, SAXS has evolved into a versatile technique for quantitatively characterizing the features and forces that govern the behavior of biomolecules in solution. This progress has been driven by the dramatically improving brightness of synchrotron radiation x-ray sources combined with the wide availability of new computational resources for interpreting SAXS measurements. This chapter uses contemporary examples to illustrate how solution SAXS provides insights into the chemical physics of proteins and nucleic acids that are difficult – in some cases, impossible – to obtain by other techniques.

The presented examples are ordered from the most straightforward analyses and applications of SAXS experiments to the most sophisticated, and include practical notes on each...


Virial Coefficient Conformational Ensemble Guanidinium Hydrochloride Interparticle Interference Biomolecule Concentration 
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  1. 1.
    Koch, M.H., Vachette, P., and Svergun, D.I. (2003) Q. Rev. Biophys., 36, 147.CrossRefGoogle Scholar
  2. 2.
    Feigin, L.A. and Svergun, D.I. (1987) Structure Analysis by Small-Angle X-ray and Neutron Scattering. Plenum Press, New York.Google Scholar
  3. 3.
    Svergun, D.I., Richard, S., Koch, M.H., Sayers, Z., Kuprin, S., and Zaccai, G. (1998) Proc. Natl. Acad. Sci. USA, 95, 2267.ADSCrossRefGoogle Scholar
  4. 4.
    Svergun, D., Barberato, C., and Koch, M.H.J. (1995) J. Appl. Cryst., 28, 768.CrossRefGoogle Scholar
  5. 5.
    Moore, P.B. (1980) J. Appl. Cryst., 13, 168.CrossRefGoogle Scholar
  6. 6.
    Svergun, D.I., Semenyuk, A.V., and Feigin, L.A. (1988) Acta Cryst., A44, 244.Google Scholar
  7. 7.
    Svergun, D.I. (1992) J. Appl. Cryst., 25, 495.CrossRefGoogle Scholar
  8. 8.
    Millett, I.S., Doniach, S., and Plaxco, K.W. (2002) Adv. Protein Chem., 62, 241.CrossRefGoogle Scholar
  9. 9.
    Kohn, J.E., Millett, I.S., Jacob, J., Zagrovic, B., Dillon, T.M., Cingel, N., Dothager, R.S., Seifert, S., Thiyagarajan, P., Sosnick, T.R., Hasan, M.Z., Pande, V.S., Ruczinski, I., Doniach, S., and Plaxco, K.W. (2004) Proc. Natl. Acad. Sci. USA, 101, 12491.ADSCrossRefGoogle Scholar
  10. 10.
    Fitzkee, N.C. and Rose, G.D. (2004) Proc. Natl. Acad. Sci. USA, 101, 12497.ADSCrossRefGoogle Scholar
  11. 11.
    Lindorff-Larsen, K., Kristjansdottir, S., Teilum, K., Fieber, W., Dobson, C.M., Poulsen, F.M., and Vendruscolo, M. (2004) J. Am. Chem. Soc., 126, 3291.CrossRefGoogle Scholar
  12. 12.
    Segel, D.J., Fink, A.L., Hodgson, K.O., and Doniach, S. (1998) Biochemistry, 37, 12443.CrossRefGoogle Scholar
  13. 13.
    Fang, X.W., Yang, X.J., Littrell, K., Niranjanakumari, S., Thiyagarajan, P., Fierke, C.A., Sosnick, T.R., and Pan, T. (2001) RNA, 7, 233.CrossRefGoogle Scholar
  14. 14.
    Bonnete, F. and Vivares, D. (2002) Acta Cryst., D58, 1571.Google Scholar
  15. 15.
    Vivares, D. and Bonnete, F. (2002) Acta Cryst., D58, 472.Google Scholar
  16. 16.
    Skibinska, L., Gipinski, J., Liu, H., Patkowski, A., Fischer, E.W., and Pecora, R. (1999) J. Chem. Phys., 1794.Google Scholar
  17. 17.
    Chacon, P., Moran, F., Diaz, J.F., Pantos, E., and Andreu, J.M. (1998) Biophys. J., 74, 2760.ADSCrossRefGoogle Scholar
  18. 18.
    Walther, D., Cohen, D., and Doniach, S. (2000) J. Appl. Cryst., 33, 350.CrossRefGoogle Scholar
  19. 19.
    Svergun, D. (1999) Biophys. J., 76, 2879.ADSCrossRefGoogle Scholar
  20. 20.
    Svergun, D.I., Petoukhov, M.V., and Koch, M.H.J. (2001) Biophys. J., 80, 2946.CrossRefGoogle Scholar
  21. 21.
    Stuhrmann, H.B. (1970) Acta Cryst., A26, 297.Google Scholar
  22. 22.
    Takahashi, Y., Nishikawa, Y., and Fujisawa, T. (2003) J. Appl. Cryst., 36, 549.CrossRefGoogle Scholar
  23. 23.
    Meyer, A.S., Gillespie, J.R., Walther, D., Millet, I.S., Doniach, S., and Frydman, J. (2003) Cell, 113, 369.CrossRefGoogle Scholar
  24. 24.
    Gutsche, I., Essen, L.O., and Baumeister, W. (1999) J. Mol. Biol., 293, 295.CrossRefGoogle Scholar
  25. 25.
    Funari, S.S., Rapp, G., Perbandt, M., Dierks, K., Vallazza, M., Betzel, C., Erdmann, V.A., and Svergun, D.I. (2000) J. Biol. Chem., 275, 31283.CrossRefGoogle Scholar
  26. 26.
    Harms, J., Schluenzen, F., Zarivach, R., Bashan, A., Gat, S., Agmon, I., Bartels, H., Franceschi, F., and Yonath, A. (2001) Cell, 107, 679.CrossRefGoogle Scholar
  27. 27.
    Ban, N., Nissen, P., Hansen, J., Moore, P.B., and Steitz, T.A. (2000) Science, 289, 905.ADSCrossRefGoogle Scholar
  28. 28.
    Westhof, E., Romby, P., Romaniuk, P.J., Ebel, J.P., Ehresmann, C., and Ehresmann, B. (1989) J. Mol. Biol., 207, 417.CrossRefGoogle Scholar
  29. 29.
    Grosberg, A.Y., Nguyen, T.T., and Shklovskii, B.I. (2002) Rev. Mod. Phys., 74, 329.ADSCrossRefGoogle Scholar
  30. 30.
    Bloomfield, V.A. (1997) Biopolymers, 44, 269.CrossRefGoogle Scholar
  31. 31.
    Oosawa, F. (1968) Biopolymers, 6, 134.Google Scholar
  32. 32.
    Russell, R., Millett, I.S., Tate, M.W., Kwok, L.W., Nakatani, B., Gruner, S.M., Mochrie, S.G., Pande, V., Doniach, S., Herschlag, D., and Pollack, L. (2002) Proc. Natl. Acad. Sci. USA, 99, 4266.ADSCrossRefGoogle Scholar
  33. 33.
    Das, R., Kwok, L.W., Millett, I.S., Bai, Y., Mills, T.T., Jacob, J., Maskel, G.S., Seifert, S., Mochrie, S.G., Thiyagarajan, P., Doniach, S., Pollack, L., and Herschlag, D. (2003) J. Mol. Biol., 332, 311.CrossRefGoogle Scholar
  34. 34.
    Bai, Y., Das, R., Millett, I.S., Herschlag, D., and Doniach, S. (2005) Probing counterion modulated repulsion and attraction between nucleic acid duplexes in solution. Proceedings of the National Academy of Sciences USA, 102, 959–960.Google Scholar
  35. 35.
    Murphy, M.C., Rasnik, I., Cheng, W., Lohman, T.M., and Ha, T. (2004) Biophys. J., 86, 2530.ADSCrossRefGoogle Scholar
  36. 36.
    Draper, D.E. (2004) RNA, 10, 335.CrossRefGoogle Scholar
  37. 37.
    Bram, S. and Beeman, W.W. (1971) J. Mol. Biol., 55, 311.CrossRefGoogle Scholar
  38. 38.
    Zaccai, G. and Xian, S.-Y. Biochemistry, 27, 1316.Google Scholar
  39. 39.
    Zakharova, S.S., Egelhaaf, S.U., Bhuiyan, L.B., Outhwaite, C.W., Bratko, D., and Maarel, J.R.C. van der (1999) J. Chem. Phys., 111, 10706.ADSCrossRefGoogle Scholar
  40. 40.
    Das, R., Mills, T.T., Kwok, L.W., Maskel, G.S., Millett, I.S., Doniach, S., Finkelstein, K.D., Herschlag, D., and Pollack, L. (2003) Phys. Rev. Lett., 90, 188103.ADSCrossRefGoogle Scholar
  41. 41.
    Andresen, K., Das, R., Park, H.Y., Smith, H., Kwok, L.W., Lamb, J.S., Kirkland, E.J., Herschlag, D., Finkelstein, K.D., and Pollack, L. (2004) Spatial distribution of competing ions around DNA in solution. Physical Review Letters 93, 248013.ADSCrossRefGoogle Scholar
  42. 42.
    Segel, D.J., Bachmann, A., Hofrichter, J., Hodgson, K.O., Doniach, S., and Kiefhaber, T. (1999) J. Mol. Biol., 288, 489.CrossRefGoogle Scholar
  43. 43.
    Pollack, L., Tate, M.W., Darnton, N.C., Knight, J.B., Gruner, S.M., Eaton, W.A., and Austin, R.H. (1999) Proc. Natl. Acad. Sci. USA, 96, 10115.ADSCrossRefGoogle Scholar
  44. 44.
    Akiyama, S., Takahashi, S., Kimura, T., Ishimori, K., Morishima, I., Nishikawa, Y., and Fujisawa, T. (2002) Proc. Natl. Acad. Sci. USA, 99, 1329.ADSCrossRefGoogle Scholar
  45. 45.
    Doniach, S. (2001) Chem. Rev., 101, 1763.CrossRefGoogle Scholar
  46. 46.
    Plaxco, K.W., Millett, I.S., Segel, D.J., Doniach, S., and Baker, D. (1999) Nat. Struct. Biol., 6, 554.CrossRefGoogle Scholar
  47. 47.
    Jacob, J., Krantz, B., Dothager, R.S., Thiyagarajan, P., and Sosnick, T.R. (2004) J. Mol. Biol., 338, 369.CrossRefGoogle Scholar
  48. 48.
    Russell, R., Millett, I.S., Doniach, S., and Herschlag, D. (2000) Nat. Struct. Biol., 7, 367.CrossRefGoogle Scholar
  49. 49.
    Sclavi, B., Sullivan, M., Chance, M.R., Brenowitz, M., and Woodson, S.A. (1998) Science, 279, 1940.ADSCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • R. Das
    • 1
  • S. Doniach
    • 2
  1. 1.Stanford UniversityCAUSA
  2. 2.Stanford UniversityCAUSA

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