Protein–DNA Interactions: Structure and Energetics

Tom K Kerppola, Howard Hughes Medical Institute and University of Michigan Medical School, Ann Arbor, Michigan, USA

Published online: June 2001

DOI: 10.1038/npg.els.0001349

DNA-binding proteins recognize specific DNA sequences by a combination of molecular interactions. Protein–DNA complex formation is frequently accompanied by conformational changes in one or both components of the complex. Protein–DNA interactions differ in several respects from most other ligand–receptor interactions in cells, and these characteristics place special requirements on the energetics and dynamics of protein–DNA interactions and explain many of the special properties of these complexes.

Keywords: DNA binding specificity; hydrogen bonding; electrostatic interactions; solvation; hydrophobic effect; van der Waal's forces; steric fit; conformational changes; multiprotein complexes; cooperative binding

Figure 1. Functional groups available for direct recognition in the major and minor grooves on guanine (G)–cytosine (C) and adenine (A)–thymine (T) base pairs. Hydrogen bond acceptors are indicated by diamonds and hydrogen bond donors are indicated by hourglass shapes. The methyl group on thymine is indicated by a circle. Reproduced from Jen-Jacobson (1997) © John Wiley & Sons, Inc.
Figure 2. Estimated favourable (blue) and unfavourable (red) energetic terms that contribute to the overall stabilities of complexes formed by EcoRI at specific (left) and nonspecific (right) binding sites. The contribution of DNA distortion, protein conformational changes, vibrational restrictions etc. was calculated based on the difference between the other terms. The various favourable and unfavourable contributions to binding energy are interdependent. The difference between the specific and nonspecific binding affinities represents the specificity ratio. Reproduced from Steitz (1990) © Cambridge University Press.
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 Further Reading
    Batchelor AH, Piper DE, de la Brousse FC, McKnight SL and Wolberger C (1998) The structure of GABP/: an ETS domain–ankyrin heterodimer bound to DNA. Science 279(5353): 1037–1041.
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    Jen-Jacobson L (1997) Protein–DNA recognition complexes: conservation of structure and binding energy in the transition state. Biopolymers 44: 153–180.
    Kerppola TK (1998) Transcriptional cooperativity: bending over backwards and doing the flip. Structure 6: 549–554.
    Manning GS (1978) The molecular theory of polyelectrolyte solutions with applications to the electrostatic properties of polynucleotides. Quarterly Review of Biophysics 11: 179–246.
    Martin AM, Sam MD, Reich NO and Perona JJ (1999) Structural and genetic origins of indirect readout in site-specific DNA cleavage by a restriction endonuclease. Nature Structural Biology 6: 269–277.
    Patel L, Abate C and Curran T (1990) Altered protein conformation on DNA binding by Fos and Jun. Nature 347: 572–575.
    Steitz TA (1990) Structural studies of protein–nucleic acid interaction: the sources of sequence-specific binding. Quarterly Reviews of Biophysics 23(3): 205–280.
    von Hippel PH and Berg OG (1989) Facilitated target location in biological systems. Journal of Biological Chemistry 264(2): 675–678.

Related Sub-Topics:

Protein Structure | Nucleic Acid Structure | DNA Structure and Function | Biomolecular Interactions | Nucleic Acids: Structure, Function, Metabolism
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Article Title: Protein–DNA Interactions: Structure and Energetics
 
How to Cite close
Kerppola, Tom K(Jun 2001) Protein–DNA Interactions: Structure and Energetics. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0001349]