Abstract
At high concentration (98% or higher, v/v), glycerol induces collapse of acid-denatured cytochrome c into a compact state, the GU state, showing a molten globule character. The GU state possesses a nativelike α-helix structure but a tertiary conformation less packed with respect to the native state. The spectroscopic properties of the GU state closely resemble those of the molten globule stabilized by the organic solvent from the native protein (called the GN state), indicating that glycerol can stabilize the molten globule of cytochrome c either from the native or the acid-denatured protein. The GU and the GN states show spectroscopic (and, thus, structural) properties and stabilities comparable to those of molten globules stabilized by different effectors, despite the fact that the mechanisms involved in the molten globule formation may significantly differ. This implies in cytochrome c a hierarchy for the rupture (native-to-molten globule) or the formation (unfolded-to-molten globule) of intramolecular interactions leading to the stabilization of the molten globule state of the protein, independently from the effector responsible for the structural transition, in accord with the sequential model proposed by Englander and collaborators.
Similar content being viewed by others
REFERENCES
Acharya, A. S., Iyer, K. S., Sahni, G., Khandke, K. M., and Manjula, B. N. (1992). J. Protein Chem. 11, 527-538.
Bai, Y., Sosnick, T. R., Mayne, L., and Englander, S. W. (1995). Science 269, 192-197.
Baldwin, R. L. (1991). Chemtracts-Biochem. Mol. Biol. 2, 379-389.
Barrick, D. and Baldwin, R. L. (1993). Protein Sci. 2, 869-876.
Bushnell, G. W., Louie, G. V., and Brayer, G. D. (1990). J. Mol. Biol. 214, 585-595.
Chen, Y.-H., Yang, J. T., and Martinez, H. M. (1972). Biochemistry 11, 4120-4131.
Christensen, H. and Pain, R. H. (1991). Eur. Biophys. J. 19, 221-229.
Creighton, T. E. (1990). Biochem. J. 270, 1-15.
Davis-Searles, P. R., Morar, A. S., Saunders, A. J., Erie, D. A., and Pielak, G. J. (1998). Biochemistry 37, 17048-17053.
Dill, K. A. and Chan, H. S. (1997). Nature Struct. Biol. 4, 10-19.
Dobson, C. M. (1992). Curr. Opin. Struct. Biol. 2, 6-12.
Ferri, T., Poscia, A., Ascoli, F., and Santucci, R. (1996). Biochim. Biophys. Acta 1298, 102-108.
Goto, Y. and Nishikiori, S. (1991). J. Mol. Biol. 222, 679-686.
Goto, Y., Calciano, L. J., and Fink, A. L. (1990a). Proc. Natl. Acad. Sci. U.S.A. 87, 573-577.
Goto, Y., Takahashi, N., and Fink, A. L. (1990b). Biochemistry 29, 3480-3488.
Jeng, M. F., Englander, S. W., Elove, G. A., Wand, A. J., and Roder, H. (1990). Biochemistry 29, 10433-10437.
Jordan, T., Eads, J. C., and Spiro, T. G. (1995). Protein Sci. 4, 716-728.
Kamatari, Y. O., Konno, T., Kataoka, M., and Akasaka, K. (1996). J. Mol. Biol. 259, 512-523.
Kamatari, Y. O., Konno, T., Kataoka, M., and Akasaka, K. (1998). Protein Sci. 7, 681-688.
Kamiyama, T., Sadahide, Y., Nogusa, Y., and Gekko, K. (1999). Biochim. Biophys. Acta 1434, 44-57.
Kataoka, M., Hagihara, Y., Mihara, K., and Goto, Y. (1993). J. Mol. Biol. 229, 591-596.
Kim, P. S. and Baldwin, R. L. (1990). Annu. Rev. Biochem. 59, 631-660.
Konno, T., Tanaka, N., Kataoka, M., Takano, E., and Maki, M. (1997). Biochim. Biophys. Acta 1342, 73-82.
Kornblatt, J. A., Kornblatt, M. J., Hoa, G. H., and Mauk, A. G. (1993). Biophys. J. 65, 1059-1065.
Kuwajima, K. (1989). Proteins: Struct. Funct. Genet. 6, 87-103.
Kuwajima, K. (1996). FASEB J. 10, 102-109.
Marmorino, J. L. and Pielak, G. J. (1995). Biochemistry 34, 3140-3143.
Moore, G. R. and Pettigrew, G. W. (1990). Cytochromes c. Evolutionary, Structural and Physicochemical Aspects, Springer-Verlag, Berlin and New York, Chapter 4.
Pace, C. N. (1975). CRC Crit. Rev. Biochem. 3, 1-43.
Ptytsin, O. B. (1992). In Protein Folding (Creighton, T. E., ed.), W. H. Freeman and Co., New York, pp. 243-300.
Santucci, R. and Ascoli, F. (1997). J. Inorg. Biochem. 68, 211-214.
Santucci, R., Bongiovanni, C., Mei, G., Ferri, T., Polizio, F., and Desideri, A. (2000). Biochemistry 39, 12632-12638.
Santucci, R., Polizio, F., and Desideri, A. (1999). Biochemie 81, 745-751.
Sedlák E. and Antalík, M. (1999). Biochim. Biophys. Acta 1434, 347-355.
Shiraki, K., Nishikawa, K., and Goto, Y. (1995). J. Mol. Biol. 245, 180-194.
Sosnick, T. R., Mayne, L., Hiller, R., and Englander, S. W. (1994). Nature Struct. Biol. 1, 149-156.
Stellwagen, E. and Cass, R. (1974). Biochem. Biophys. Res. Commun. 60, 371-375.
Takahashi, S., Yeh, S.-R., Das, T. K., Chan, C.-K., Gottfried, D. S., and Rousseau, D. L. (1997). Nature Struct. Biol. 4, 44-50.
Xu, Y., Mayne, L., and Englander, S. W. (1998). Nature Struct. Biol. 5, 774-778.
Yeh, S.-R., Takahashi, S., Fan, B., and Rousseau, D. L. (1997). Nature Struct. Biol. 4, 51-56.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bongiovanni, C., Sinibaldi, F., Ferri, T. et al. Glycerol-Induced Formation of the Molten Globule from Acid-Denatured Cytochrome c: Implication for Hierarchical Folding. J Protein Chem 21, 35–41 (2002). https://doi.org/10.1023/A:1014179031881
Published:
Issue Date:
DOI: https://doi.org/10.1023/A:1014179031881