Protein–DNA Interactions: Structure and Energetics

Abstract

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 © 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 © Cambridge University Press.

close

References

Chen L, Glover JNM, Hogan PG, Rao A and Harrison SC (1998) Structure of the DNA‐binding domains from NFAT, Fos and Jun bound specifically to DNA. Nature 392: 42.

Dlakić M, Grinberg AV, Leonard DA and Kerppola TK (2001) DNA sequence‐dependent folding determines the divergence in binding specificities between Maf and other bZip proteins. EMBO Journal 20: 828–840.

Diebold RJ, Rajaram N, Leonard DA and Kerppola TK (1998) Molecular basis of cooperative DNA bending and oriented heterodimer binding in the NFAT1‐Fos‐Jun‐ARRE2 complex. Proceedings of the National Academy of Sciences of the USA 95: 7915.

Honig B and Nicholls A (1995) Classical electrostatics in biology and chemistry. Science 268: 1144–1149.

Jen‐Jacobson L (1997) Protein–DNA recognition complexes: conservation of structure and binding energy in the transition state. Biopolymers 44: 153–180.

Kerppola TK and Curran T (1991) DNA bending by Fos and Jun: the flexible hinge model. Science 254: 1210–1214.

Ladbury JE, Wright JG, Sturtevant JM and Sigler PB (1994) A thermodynamic study of the trp repressor‐operator interaction. Journal of Molecular Biology 238: 669–681.

Leonard DA and Kerppola TK (1998) DNA bending determines Fos‐Jun heterodimer orientation. Nature Structural Biology 5: 877.

Leonard DA, Rajaram N and Kerppola TK (1997) Structural basis of DNA bending and oriented heterodimer binding by Fos and Jun. Proceedings of the National Academy of Sciences of the USA 94: 4913–4918.

Manning GS (1978) The molecular theory of polyelectrolyte solutions with applications to the electrostatic properties of polynucleotides. Quarterly Review of Biophysics 11: 179–246.

Patel L, Abate C and Curran T (1990) Altered protein conformation on DNA binding by Fos and Jun. Nature 347: 572–575.

Ramirez‐Carrozzi VR and Kerppola TK (2001a) Long‐range electrostatic interactions influence the orientation of Fos–Jun binding at AP‐1 sites. Journal of Molecular Biology 305: 411–427.

Ramirez‐Carrozzi VR and Kerppola TK (2001b) Dynamics of Fos–Jun–NFAT1 complexes. Proceedings of the National Academy of Sciences of the USA 98: 4893–4898.

Spolar RS and Record MT Jr (1994) Coupling of local folding to site‐specific binding of DNA proteins. Science 263: 777–784.

Tan S and Richmond TJ (1998) Crystal structure of the yeast MAT‐alpha2/MCM1/DNA ternary complex. Nature 391: 660.

Further Reading

Batchelor AH, Piper DE, de la Brousse FC, McKnight SL and Wolberger C (1998) The structure of GABPα/β: an ETS domain–ankyrin heterodimer bound to DNA. Science 279(5353): 1037–1041.

Honig B and Nicholls A (1995) Classical electrostatics in biology and chemistry. Science 268: 1144–1149.

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.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

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]