Abstract
Conformational changes, and the formation of densely packed ordered aggregates or crystals, are behaviors that profoundly affect the properties of a molecule. Using the example of biological macromolecules, we discuss two types of interactions between these two behaviors. First, we demonstrate that shape change may be driven by crystallization if the gain in crystallization free energy is sufficient to overcome the transition to an unfavorable molecular conformation. Hence, the crystal structures of flexible molecules may be a poor representation of their free-phase atomic arrangements. Second, molecules with conformational variability, such as proteins, may facilitate the nucleation of their crystals by forming dense liquid clusters enriched in domain-swapped or misassembled oligomers. In the clusters, the nucleation barrier is reduced due to the lower surface free energy of the crystal/dense liquid interface, and nucleation is significantly faster.
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References
J. Trotter, Acta Crystallogr. 14, 1135 (1961).
A. Almenningen, O. Bastiansen, L. Fernholt, B.N. Cyvin, S.J. Cyvin, S. Samdal, J. Mol. Struct. 128, 59 (1985).
N.E. Chayen, J.R. Helliwell, E.H. Snell, “Macromolecular Crystallization and Crystal Perfection,” IUCr Monographs on Crystallography, 24 ( Oxford University Press, Oxford, New York, 2010).
T. Bergfors, Ed., Protein Crystallization, 2nd ed. ( International University Line, La Jolla, CA, 2009).
J.D. Ng, Y.G. Kuznetsov, A.J. Malkin, G. Keith, R. Giege, A. McPherson, Nucleic Acids Res. 25, 2582 (1997).
A. McPherson, Crystallization of Biological Macromolecules (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1999 ).
A.J. Malkin, R.E. Thorne, Methods 34, 273 (2004).
P. Vekilov, “Nucleation and Growth Mechanisms of Protein Crystals,” in Handbook of Crystal Growth, T. Nishinaga, Ed. (Elsevier, Amsterdam, 2015), vol. 1, p. 795.
D.L. Nelson, M.M. Cox, Lehninger’s Principles of Biochemistry, 3rd ed. (W.H. Freeman, New York, 2000).
A. Ducruix, R. Giege, Eds., Crystallization of Nucleic Acids and Proteins: A Practical Approach (IRL Press, Oxford, 1992).
Y. Devedjiev, Acta Crystallogr. F Struct. Biol. Cryst. Commun. 71, 157 (2015).
K. Wütrich, Acta Crystallogr. D Biol. Crystallogr. 51, 249 (1995).
A.A. Yee, A. Savchenko, A. Ignachenko, J. Lukin, X. Xu, T. Skarina, E. Evdokimova, C.S. Liu, A. Semesi, V. Guido, A.M. Edwards, C.H. Arrowsmith, J. Am. Chem. Soc. 127, 16512 (2005).
C.R.R. Grace, M.H. Perrin, J. Gulyas, M.R. DiGruccio, J.P. Cantle, J.E. Rivier, W.W. Vale, R. Riek, Proc. Natl. Acad. Sci. U.S.A. 104, 4858 (2007).
H.M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T.N. Bhat, H. Weissig I.N. Shindyalov, P.E. Bourne, Nucleic Acids Res. 28, 235 (2000).
C.K. Fisher, C.M. Stultz, Curr. Opin. Struct. Biol. 21, 426 (2011).
S.O. Garbuzynskiy, B.S. Melnik, M.Y. Lobanov, A.V. Finkelstein, O.V. Galzitskaya, Proteins Struct. Funct. Bioinform. 60, 139 (2005).
C. Bissantz, P. Bernard, M. Hibert, D. Rognan, Proteins Struct. Funct. Bioinform. 50, 5 (2003).
M. Kontoyianni, L.M. McClellan, G.S. Sokol, J. Med. Chem. 47, 558 (2004).
K.L. Meagher, H.A. Carlson, J. Am. Chem. Soc. 126, 13276 (2004).
N.M.F.S.A. Cerqueira, N.F. Bras, P.A. Fernandes, M.J. Ramos, Proteins Struct. Funct. Bioinform. 74, 192 (2009).
M.P. Schlunegger, M.J. Bennett, D. Eisenberg, Adv. Protein Chem. 50, 61 (1997).
M.J. Bennett, M.P. Schlunegger, D. Eisenberg, Protein Sci. 4, 2455 (1995).
I. Zegers, J. Deswarte, L. Wyns, Proc. Natl. Acad. Sci. U.S.A. 96, 818 (1999).
Y. Liu, P.J. Hart, M.P. Schlunegger, D. Eisenberg, Proc. Natl. Acad. Sci. U.S.A. 95, 3437 (1998).
S. Hirota, Y. Hattori, S. Nagao, M. Taketa, H. Komori, H. Kamikubo, Z. Wang, I. Takahashi, S. Negi, Y. Sugiura, M. Kataoka, Y. Higuchi, Proc. Natl. Acad. Sci. U.S.A. 107, 12854 (2010).
A. McPherson, Introduction to Macromolecular Crystallography (Wiley, Hoboken, NJ, 2009).
A.A. Chernov, H. Komatsu, “Principles of Crystal Growth in Protein Crystallization,” in Science and Technology of Crystal Growth, J.P. van der Eerden, O.S.L. Bruinsma, Eds. (Kluwer Academic, Dordrecht, The Netherlands, 1995), p. 329.
P.G. Vekilov, Cryst. Growth Des. 7, 2796 (2007).
D.N. Petsev, K. Chen, O. Gliko, P.G. Vekilov, Proc. Natl. Acad. Sci. U.S.A. 100, 792 (2003).
S.-T. Yau, B.R. Thomas, P.G. Vekilov, Phys. Rev. Lett. 85, 353 (2000).
S.-T. Yau, D.N. Petsev, B.R. Thomas, P.G. Vekilov, J. Mol. Biol. 303, 667 (2000).
Z. Derewenda, Structure 12, 529 (2004).
Z.S. Derewenda, Acta Crystallogr. D Biol. Crystallogr. 66, 604 (2010).
Z.S. Derewenda, P.G. Vekilov, Acta Crystallogr. D Biol. Crystallogr. 62, 116 (2006).
A.J. Malkin, Y.G. Kuznetsov, W. Glanz, A. McPherson, J. Phys. Chem. 100, 11736 (1996).
I. Reviakine, D.K. Georgiou, P.G. Vekilov, J. Am. Chem. Soc. 125, 11684 (2003).
S.-T. Yau, P.G. Vekilov, Nature 406, 494 (2000).
J.W. Gibbs, Trans. Connect. Acad. Sci. 3, 108 (1876).
J.W. Gibbs, Trans. Connect. Acad. Sci. 3, 343 (1878).
O. Galkin, P.G. Vekilov, Proc. Natl. Acad. Sci. U.S.A. 97, 6277 (2000).
P.G. Vekilov, Cryst. Growth Des. 4, 671 (2004).
W. Pan, A.B. Kolomeisky, P.G. Vekilov, J. Chem. Phys. 122, 174905 (2005).
P.G. Vekilov, Cryst. Growth Des. 10, 5007 (2010).
A.J. Malkin, A. McPherson, J. Cryst. Growth 128, 1232 (1993).
A.J. Malkin, A. McPherson, Acta Crystallogr. D Biol. Crystallogr. 50, 385 (1994).
P.G. Vekilov, Nat. Nanotechnol. 6, 82 (2011).
S.-T. Yau, P.G. Vekilov, J. Am. Chem. Soc. 123, 1080 (2001).
O. Galkin, P.G. Vekilov, J. Am. Chem. Soc. 122, 156 (2000).
J.W. Gibbs, The Scientific Papers of J. Willard Gibbs, Vol. One: Thermodynamics (Oxbow Press, Woodbridge, CT, 1993).
Y. Li, V. Lubchenko, M.A. Vorontsova, L. Filobelo, P.G. Vekilov, J. Phys. Chem. B 116, 10657 (2012).
O. Gliko, W. Pan, P. Katsonis, N. Neumaier, O. Galkin, S. Weinkauf, P.G. Vekilov J. Phys. Chem. B 111, 3106 (2007).
M. Sleutel, A.E. Van Driessche, Proc. Natl. Acad. Sci. U.S.A. 111, E546 (2014).
D. Maes, M.A. Vorontsova, M.A.C. Potenza, T. Sanvito, M. Sleutel, M. Giglio, P.G. Vekilov, Acta Crystallogr. F Struct. Biol. Cryst. Commun. 71, 815 (2015).
O. Gliko, N. Neumaier, W. Pan, I. Haase, M. Fischer, A. Bacher, S. Weinkauf, P.G. Vekilov, J. Am. Chem. Soc. 127, 3433 (2005).
W. Pan, O. Galkin, L. Filobelo, R.L. Nagel, P.G. Vekilov, Biophys. J. 92, 267 (2007).
W. Pan, P.G. Vekilov, V. Lubchenko, J. Phys. Chem. B 114, 7620 (2010).
M.J. Bennett, M.R. Sawaya, D. Eisenberg, Structure 14, 811 (2006).
W. Royer Jr., “Structures of Red Blood Cell Hemoglobins,” in Blood and Tissue Oxygen Carriers, Ch.P. Mangum, Ed. (Springer, Berlin, 1992), p. 87.
S.H. Bhosale, M.B. Rao, V.V. Deshpande, Microbiol. Rev. 60, 280 (1996).
P. Srivastava, S. Shukla, S.K. Choubey, V.S. Gomase, J. Enzyme Res. 1, 1 (2010).
M.A. Vorontsova, D. Maes, P.G. Vekilov, Faraday Discuss. 179, 27 (2015).
P.G. Vekilov, M.A. Vorontsova, Acta Crystallogr. F Struct. Biol. Cryst. Commun. 70, 271 (2014).
S.V. Albers, B.H. Meyer, Nat. Rev. Microbiol. 9, 414 (2011).
U.B. Sleytr, P. Messner, D. Pum, M. Sara, Angew. Chem. Int. Ed. 38, 1035 (1999).
M. Stewart, T.J. Beveridge, T.J. Trust, J. Bacteriol. 166, 120 (1986).
S. Chung, S.H. Shin, C.R. Bertozzi, J.J. De Yoreo, Proc. Natl. Acad. Sci. U.S.A. 107, 16536 (2010).
S.H. Shin, S. Chung, B. Sanii, L.R. Comolli, C.R. Bertozzi, J.J. De Yoreo, Proc. Natl. Acad. Sci. U.S.A. 109, 12968 (2012).
S.-H. Kim, D.H. Shin, J. Liu, V. Oganesyan, S. Chen, Q.S. Xu, J.-S. Kim, D. Das, U. Schulze-Gahmen, S.R. Holbrook, E.L. Holbrook, B.A. Martinez, N. Oganesyan, A. DeGiovanni, Y. Lou, M. Henriquez, C. Huang, J. Jancarik, R. Pufan, N.-G. Choi, J.-M. Chandonia, J. Hou, B. Gold, H. Yokota, S.E. Brenner P.D. Adams, R. Kim, J. Struct. Funct. Genomics 6, 63 (2005).
A.N. Naganathan, V. Munoz, J. Am. Chem. Soc. 127, 480 (2005).
Acknowledgements
P.G.V. and K.N.O. were supported by NASA (Grants NNX14AD68G and NNX14AE79G) and NSF (Grant MCB-1244568). S.W.C. gratefully acknowledges support by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Korea (NRF-2015R1D1A1A01059580) and Pusan National University Research Grant, 2014.
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Vekilov, P.G., Chung, S. & Olafson, K.N. Shape change in crystallization of biological macromolecules. MRS Bulletin 41, 375–380 (2016). https://doi.org/10.1557/mrs.2016.87
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DOI: https://doi.org/10.1557/mrs.2016.87