Abstract
In this paper we describe a number of approaches to the nature and specificity of DNA-protein interactions involved in the regulation of gene expression at the transcriptional level. We discuss primarily the binding of ‘single-specific-site’ regulatory proteins to DNA targets. This involves consideration of several aspects of the specificity of DNA-protein interactions, including: (1) the combinatorial specification of the number of base pairs required to define a unique binding site in a genome of given size; (2) the structure of DNA and protein binding sites, including structural complementarity and steric aspects; (3) the energetics of the binding interaction, including both specific and non-specific binding; (4) the thermodynamics and kinetics of the overall interaction, as determined by the net binding free energy of specific complex formation and the effects of competing sites; and (5) equilibrium binding selection, which determines the actual level of saturation of the specific (regulatory) target under various environmental conditions. These aspects are all interdependent, and a coherent picture of the specificity of such interactions can be obtained only by considering them all in context. Such an approach has been set forth by us previously, in part, in von Hippel and Berg (1986), and portions of this overview are taken directly from that treatment. In conclusion, we consider how these ideas modulate the evolutionary ‘design’ of regulatory proteins, as well as the formulation of purification procedures and binding assays for these proteins, and how these approaches may apply in vivo.
This is a preview of subscription content, log in via an institution.
Preview
Unable to display preview. Download preview PDF.
References
Anderson, J. E., Ptashne, M. and Harrison, S. C. (1987). Structure of the repressor-operator complex of bacteriophage 434. Nature, 326, 846–852
Berg, O. G. and von Hippel, P. H. (1987). Selection of DNA binding sites by regulatory proteins. Statistical-mechanical theory and applications to operators and promoters. J.Mol. Biol., 193, 723–750
Berg, O. G. and von Hippel, P. H. (1988). Selection of DNA binding sites by regulatory proteins. II. The binding specificity of cyclic AMP receptor protein (CRP) to recognition sites. J. Mol. Biol., in press
Berg, O. G., Winter, R. B. and von Hippel, P. H. (1982). How do genome-regulatory proteins locate their DNA target sites? Trends Biochem. Sci., 7, 52–55
deHaseth, P. L., Lohman, T. M. and Record, M. T., Jr (1977). Nonspecific interaction of lac repressor with DNA: an association reaction driven by counterion release. Biochemistry, 16, 4783–4790
deHaseth, P. L. Lohman, T. M., Record, M. T., Jr and Burgess, R. R. (1978). Nonspecific interactions of Escherichia coli RNA polymerase with native and denatured DNA: differences in the binding behavior of core and holoenzyme. Biochemistry, 17, 1612–1622
Dickson, R. C., Abelson, J. N., Barnes, W. M. and Reznikoff, W. S. (1975). Genetic regulation. lac control region. Science, 182, 27–35
Fairfield, F. R., Newport, J. W., Dolejsi, M. K. and von Hippel, P. H. (1983). On the processivity of DNA replication. J. Biomol. Struct. Dyn., 1, 715–727
Goeddel, D. V., Yansura, D. G. and Caruthers, M. H. (1978). How lac repressor recognizes lac operator. Proc. Natl Acad. Sci. USA, 75, 3578–3582
Kopka, M. L., Yoon, C., Goodsell, D., Pjura, P. and Dickerson, R. E. (1985). The molecular origin of DNA-drug specificity in netropsin and distamycin. Proc. Natl Acad. Sci. USA, 82, 1376–1380
Kowalczykowski, S. C., Lonberg, N., Newport, J. W. and von Hippel, P. H. (1981). Interactions of T4 coded gene 32-protein with nucleic acids. I. Characterization of the binding interactions. J. Mol. Biol., 145, 75–104
Liu-Johnson, H.-N., Gartenberg, M. R. and Crothers, D. M. (1986). The DNA binding domain and bend angle of E. coli CAP protein. Cell, 47, 995–1005
Melchior, W. B., Jr and von Hippel, P. H. (1973). Alteration of the relative stability of dA · dT and dG · dC base pairs in DNA. Proc. Natl Acad. Sci. USA, 70, 298–302
Mossing, M. C. and Record, M. T., Jr (1985). Thermodynamic origins of specificity in the lac repressor-operator interactions. Adaptability in the recognition of mutant operator sites. J. Mol. Biol., 186, 295–305
O’Gorman, R. B., Rosenberg, J. M., Kallai, O. B., Dickerson, R. E., Itakura, K., Riggs, A. D. and Matthews, K. S. (1980). Equilibrium binding of inducer to lac repressor-operator DNA complex. J. Biol. Chem., 255, 10107–10114
Ohlendorf, D. H., Anderson, W. F., Fisher, R. G., Takeda, Y. and Matthews, B. W. (1982). The molecular basis of DNA-protein recognition inferred from the structure of cro repressor. Nature, 298, 718–723
Ptashne, M., Jeffrey, A., Johnson, A. D., Maurer, R., Meyer, B. J., Pabo, C. O., Roberts, T. M. and Sauer, R. T. (1980). How the λ repressor and cro work. Cell, 19, 1–11
Record, M. T., Jr, deHaseth, P. L. and Lohman, T. M. (1977). Interpretation of monovalent and divalent cation effects on the lac repressor-operator interaction. Biochemistry, 16, 4791–4796
Record, M. T., Jr, Lohman, T. M. and deHaseth, P. L. (1976). Ion effects on ligand-nucleic acid interactions. J. Mol. Biol., 107, 145–158
Revzin, A. and von Hippel, P. H. (1977). Direct measurement of association constants for the binding of Escherichia coli lac repressor to non-operator DNA. Biochemistry, 16, 4769–4776
Schneider, T. D., Stormo, G. D., Gold, L. and Ehrenfeucht, A. (1986). Information content of binding sites on nucleotide sequences. J. Mol. Biol., 188, 415–431
Seeman, N. C. Rosenberg, J. M. and Rich, A. (1976). Sequence-specific recognition of double-helical nucleic acids by proteins. Proc. Natl Acad. Sci. USA, 73, 804–808
Tronrud, D. E., Holden, H. M. and Matthews, B. W. (1987). Structures of two thermolysin-inhibitor complexes that differ by a single hydrogen bond. Science, 235, 571–574
von Hippel, P. H. (1979). On the molecular bases of the specificity of interaction and transcriptional proteins with genome DNA. In Goldberger, R. F. (ed.), Biological Regulation and Development, Plenum, New York, 279–347
von Hippel, P. H., Bear, D. G., Winter, R. B. and Berg, O. G. (1982). Molecular aspects of promoter function: An overview. In Chamberlain, M. and Rodriquez, R. (eds), Promoters: Structure and Function, Praeger, New York, 3–33
von Hippel, P. H. and Berg, O. G. (1986). On the specificity of DNA-protein interactions. Proc. Natl Acad. Sci.USA, 83, 1608–1612
von Hippel, P. H. and Berg, O. G. (1989). Facilitated target location in biological systems. J. Biol. Chem., 264, 675–678 (minireview)
von Hippel, P. H. and Fairfield, F. R. (1985). Thermodynamic aspects of the regulation of protein synthesis in bacteria. Pure Appl. Chem., 57, 45–56
von Hippel, P. H. and McGhee, J. D. (1972). DNA-protein interactions. Ann. Rev. Biochem., 41, 231–300
von Hippel, P. H., Revzin, A., Gross, C. A. and Wang, A. C. (1974). Non-specific DNA binding of genome regulating proteins as a biological control mechanism. I. The lac Operon: Equilibrium aspects. Proc. Natl Acad. Sci. USA, 71, 4808–4812
Weintraub, H. and Groudine, M. (1976). Chromosomal subunits in active genes have an altered conformation. Science, 193, 848–856
Winter, R. B., Berg, O. G. and von Hippel, P. H. (1981). Diffusion-driven mechanisms of protein translocation on nucleic acids. III. The E. coli lac repressor-operator interaction: Kinetic measurements and conclusions. Biochemistry, 20, 6961–6977
Winter, R. B. and von Hippel, P. H. (1981). Diffusion-driven mechanisms of protein translocation on nucleic acids. II. The E. coli lac repressor-operator interaction: equilibrium measurements. Biochemistry, 20, 6948–6960
Woodbury, C. P., Jr, Hagenbuchle, O. and von Hippel, P. H. (1980). DNA site recognition and reduced specificity of the EcoRI endonuclease. J. Biol. Chem., 255, 11534–11546
Woodbury, C. P., Jr and von Hippel, P. H. (1981). Relaxed sequence specificities of EcoRI endonuclease and methylase: Mechanisms, possible practical applications and uses in defining protein-nucleic acid recognition mechanisms. In Chirikjian, J. (ed.), The Restriction Enzymes, Elsevier, Amsterdam, 181–207
Yarus, M. (1969). Recognition of nucleotide sequences. Ann. Rev. Biochem., 38, 841–880
Editor information
Editors and Affiliations
Copyright information
© 1989 The Contributors
About this chapter
Cite this chapter
von Hippel, P.H., Berg, O.G. (1989). DNA-protein interactions in the regulation of gene expression. In: Saenger, W., Heinemann, U. (eds) Protein-Nucleic Acid Interaction. Topics in Molecular and Structural Biology. Palgrave, London. https://doi.org/10.1007/978-1-349-09871-2_1
Download citation
DOI: https://doi.org/10.1007/978-1-349-09871-2_1
Publisher Name: Palgrave, London
Print ISBN: 978-1-349-09873-6
Online ISBN: 978-1-349-09871-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)