Abstract
It is well established that many small, globular proteins undergo a two-state unfolding transition that is closely similar to first-order phase transitions in macroscopic systems. In such transitions the protein exists in just two detectable states, native and denatured, separated by an eneregy barrier; all the intermediate states are unstable and only transiently populated. The two-state model has been extraordinarily successful in accounting for the equilibrium denaturation behavior of proteins. However, tantalizing suggestions have appeared that this model is insufficient. Experimental evidence for residual structure in the denatured state has been accumulating for many years. Recently, for instance, changes in the amount and type of residual structure in large fragments of staphylococccal nuclease (nuclease) have been observed upon mutation or varying solvent conditions (Shortle & Meeker, 1989). Acid denatured nuclease also appears to have residual structure (Nakano & Fink, 1990). The importance and relevance of these observations to the stability and structure of nuclease, and of proteins in general, has been subject to question.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Alonso, D. O. V., Dill, K. A., Stigter, D. 1991. The three states of globular proteins: acid denaturation. Biopolym. 31: 1631–1649.
Amit, D. J. 1984. “Field Theory, the Renormalization Group, and Critical Phenomena,” Revised 2nd Ed., World Scientific Publishing, Singapore.
Barber, M. M. 1983. Finite-Size Scaling, in: “Phase Transitions and Critical Phenomena,” Vol. VII, Domb, C. & Lebowitz, J. L., eds., Academic Press, New York, 146–266.
Cialla, M. S. S., Landau, D. P. & Binder, K. 1986. Finite-size effects at temperature-driven first-order transitions. Phys. Rev. B 34: 1841–1852.
Chan, H. S. & Dill, K. A. 1991. Polymer principles in protein structure and stability. Annu. Rev. Biophys. Biophys. Chem. 20: 447–490.
Dill, K. A. & Shortle, D. 1991. Denatured states of proteins. Annu. Rev. Biochem. 60: 795–825.
Finkelstein, A. V. & Shakhnovich, E. I. 1989. Theory of cooperative transitions in protein molecules. II. Phase diagram for a protein molecule in solution. Biopolym. 28: 1681–1694.
Flanagan, J. M., Kataoka, M., Shortle, D. & Engelman, D. 1992. Truncated staphylococcal nuclease is compact but disordered. Proc. Nat. Acad. Sci. 89: 748–752.
Gittis, G.G., Stites, W. & Lattman, E.E. A first-order phase transition between a compact denatured state and a random coil state in staphylococcal nuclease. Biochemistry. In the press.
Hynes, T. R. & Fox, R. O. 1991. The crystal structure of staphylococcal nuclease refined at 1.7 Å resolution. Prot. Struct. Funct. Genet. 10: 92–105.
Ikegami, A. 1977. Structural changes and fluctuations of proteins. I A statistical thermodynamic model. Biophys. Chem. 6: 117–130.
Ikegami, A. 1981. Statistical thermodynamics of proteins and protein denaturation. Adv. Chem. Phys. 46: 363–413.
Karplus, M. & Shakhnovich, E. 1992. Protein Folding: Theoretical Studies of Thermodynamics and Dynamics, in: “Protein Folding,” Creighton, T. E., ed., W. H. Freeman, New York, 127–195.
Kim, P. S. & Baldwin, R. L. 1990. Intermediates in the folding reactions of small proteins. Annu. Rev. Biochem. 59: 631–660.
Kuwajima, K. 1992. Protein folding in vitro. Curr. Opinion in Biotechnology 3: 462–467.
Kuwajima, K. 1989. The molten globule as a clue for understanding the folding and cooperativity of globular-protein structure. Proteins: Struct., Funct., Genet. 6: 87–103.
Landau, D. P. 1990. Monte Carlo Studies Of Finite Size Effects At First And Second-Order Phase Transitions, in: “Finite Size Scaling and Numerical Simulations of Statistical Systems,” Privman, V., ed. World Scientific Publishing, Singapore, 223–260.
Loll, P. J. & Lattman, E. E. 1989. The crystal structure of the ternary complex of staphylococcal nuclease, Ca2+, and the inhibitor pdTp, refined at 1.65 Å. Proteins, Struct, Funct., Genet. 5: 183–201.
Nakano, T. & Fink, A. L. 1990. The folding of staphylococcal nuclease in the presence of methanol or guanidine thiocyanate. J. Biol. Chem. 265: 12356–12362.
Pathria, R. K. 1984. “Statistical Mechanics,” Peragamon Press, New York.
Privalov, P. L. 1979. Stability of proteins. Small globular proteins. Adv. Prot. Chem. 33: 167–241.
Ptitsyn, O. G. 1992. The Molten Globule State, in: “Protein Folding,” Creighton, T. E., ed., W. H. Freeman, New York, 243–300.
Shakhnovich, E. I. & Finkelstein, A. V. 1989. Theory of cooperative transitions in protein molecules. I. Why denaturation of globular protein is a first-order phase transition. Biopolym. 28: 1667–1680.
Shortle, D., Meeker, A. K., Freire, E. 1988. Stability mutants of staphylococcal nuclease: large compensating enthalpy-entropy changes for the reversible denaturation reaction. biochem. 27: 4761–4768.
Shortle, D. & Meeker, A. K. 1989. Residual structure in large fragments of staphylococcal nuclease: effects of amino acid substitutions. Biochem. 28: 936–944.
Shortle, D., Stites, W. E. & Meeker, A. K. 1990. Contributions of the large hydrophobic amino acids to the stability of staphylococcal nuclease. Biochem. 29: 8033–8041.
Stites, W. E., Gittis, A. G., Lattman, E. E., Shortle, D. 1991. In a staphylococcal nuclease mutant the side-chain of a lysine replacing valine 66 is fully buried in the hydrophobic core. J. Mol. Biol. 221: 7–14.
Yutani, K., Ogasahara, K., Kuwajima, K. 1992. Absence of the thermal transition in apo-ctlactalbumin in the molten globule state. J. Mol. Biol. 228: 47–350.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1994 Springer Science+Business Media New York
About this chapter
Cite this chapter
Gittis, A.G., Stites, W.E., Lattman, E.E. (1994). A First-Order Phase Transition Between a Compact Denatured State and a Random Coil State in Staphylococcal Nuclease. In: Doniach, S. (eds) Statistical Mechanics, Protein Structure, and Protein Substrate Interactions. NATO ASI Series, vol 325. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1349-4_5
Download citation
DOI: https://doi.org/10.1007/978-1-4899-1349-4_5
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4899-1351-7
Online ISBN: 978-1-4899-1349-4
eBook Packages: Springer Book Archive