Selected and Directed Mutants of T4 Phage Lysozyme
The lysozyme from bacteriophage T4 is being used as a model system to determine the factors that influence the folding and stability of proteins. The three-dimensional structure of the protein is known and lysozymes with modified properties arising from single amino acid substitutions have been obtained by classical selection techniques as well as by site-directed mutagenesis. By rationalizing the stabilities of the mutant proteins in terms of their observed three-dimensional structures we are attempting to quantitate the contributions that single amino acids make to protein stability. Our studies to date lead to the following conclusions. (1) Thermal stability is global. (2) Different types of interaction contribute to stability. (3) Changes in stability need not be associated with large structural changes. (4) An increase in the stability of an α-helix may enhance the stability of the protein as a whole. (5) Hydrogen bonds contribute to stability. (6) Protein structures can readily adjust to changes in amino acid sequence.
KeywordsAmino Acid Substitution Hydrogen Bond Network Single Amino Acid Substitution Mutant Structure Open Bond
Unable to display preview. Download preview PDF.
- 3.T. Alber, T. M. Gray, L. H. Weaver, J. Bell, J. A. Wozniak, K. Wilson, S. Daopin, and B. W. Matthews, P&S Biomedical Sciences Symposia. “Biological Organization: Macromolecular Interactions at High Resolution”. R.M. Burnett and H.J. Vogel, eds. In press (1985).Google Scholar
- 5.L. H. Weaver and B. W. Matthews, J. Mol. Biol., submitted.Google Scholar
- 8.M. G. Grütter, L. H. Weaver, T. Gray, and B. W. Matthews, In “Bacteriophage T4” (C. K. Matthews, E. Kutter, G. Mosig, P. Berget, eds), pp. 356–360. American Society for Microbiology, Washington, D.C. (1983).Google Scholar
- 9.M. G. Grütter, L. H. Weaver, T. Alber, T. M. Gray, and B. W. Matthews, Manuscript in preparation.Google Scholar
- 10.T. Alber, M. G. Grütter, T. M. Gray, J. A. Wozniak, L. H. Weaver, B-L. Chen, E. N. Baker, and B. W. Matthews, UCLA Symposium on Molecular and Cellular Biology, Protein Structure, Folding and Design. Alan R.Liss, in press (1985).Google Scholar
- 12.T. Alber, D. Muchmore, and B. W. Matthews, Manuscript in preparation.Google Scholar
- 13.D. C. Muchmore, C. B. Russell, and F. W. Dahlquist, Manuscript in preparation.Google Scholar
- 15.M. F. Schmid, L. H. Weaver, M. A. Holmes, M. G. Grütter, D. H. Ohlendorf, R. A. Reynolds, S. J. Remington, and B. W. Matthews, Acta Crystallogr. A37 : 701 (1981).Google Scholar
- 21.T. Alber and B. W. Matthews, In Protein Modification and Design, Alan R. Liss, Inc. In press.Google Scholar