Protein–DNA Interactions

Abstract

The control of the information stored in the genome is managed by DNA‐binding proteins, which are therefore of fundamental importance to cellular life. A wide diversity of such proteins, exhibiting various DNA‐binding modes, specificities and functions, is observed in living organisms. We start by describing the various roles that are played by DNA‐binding proteins, from transcription regulation to DNA repair, and review the types of molecular interactions that stabilise the protein–DNA complexes. We also describe the main structural DNA‐binding protein motifs, among which are the well‐known HTH (helix‐turn‐helix) motifs and zinc fingers, that are recurrently observed in proteins of various functions and origin. Finally, we discuss the different ways in which proteins acquire their specificity for a given DNA sequence, conformation and/or topology.

Key Concepts

  • DNA‐binding proteins have a fundamental role in the maintenance of genetic material and in the regulation of gene expression.
  • Most DNA‐binding proteins bind DNA through recurrent structural motifs.
  • The protein–DNA affinity is achieved through non‐specific interactions between amino acids and the DNA backbone and through specific interactions between amino acids and DNA bases.
  • Some proteins recognise specific DNA sequences owing to favourable direct interactions between amino acids and nucleobases.
  • Some proteins recognise specific local or global DNA conformations or topologies.

Keywords: protein–DNA binding; protein–DNA specificity; structural DNA‐binding motifs; direct/indirect readout; base/shape recognition

Figure 1. (a) Space‐filling model of the phage 434 Cro repressor in complex with the OR1 DNA operator (PDB ID: 3CRO). The α‐helices of the protein are in magenta and the coil regions in yellow; one DNA strand is depicted in green and the other in blue. The protein is drawn in transparency as a ribbon. (b) Close‐up view of the same structure showing the specific interactions at the protein–DNA interface, that is, three hydrogen bonds (depicted as dashed red lines) and one amino–π interaction (dashed light‐blue lines). The residues involved in these specific interactions are labelled and their carbon atoms coloured in green. The combination of amino/cation–π and hydrogen bonding represents a stair‐shaped motif that is recurrent at protein–DNA interfaces (Rooman ., ). In the major groove, the glutamine side chain has the adequate hydrogen donor/acceptor geometry to specifically recognise adenine (Seeman ., ).
Figure 2. (a,b) Main families of DNA‐binding protein domains. The proteins are represented as coloured ribbons and the DNA as brown sticks. Zinc ions are depicted as yellow spheres. Some representative members are depicted for each family; their PDB IDs and names are specified.
Figure 3. (a) An example of heteromultimeric protein–DNA complex, consisting of the DNA‐binding domain of NFAT1 (nuclear factor of activated T cells 1), Fos and Jun bound to DNA (PDB ID: 1A02). Proteins are depicted in orange (NFAT1), green (Fos) and blue (Jun) ribbons. The DNA molecule is represented with sticks using the following colour scheme: carbon in grey, oxygen in red, nitrogen in blue and phosphorus in orange. (b) Close‐up view of the structure showing the specific interactions at the protein–DNA interface. Hydrogen bonds are shown as dashed red lines and cation–π and amino–π interactions as dashed light‐blue lines. The residues involved in these specific interactions are labelled and their carbon atoms coloured in green. As seen in the figure, the double hydrogen bond patterns of arginine–guanine and glutamine–adenine are perfectly complementary in their donor/acceptor geometries (Seeman ., ). The consecutive occurrence of hydrogen bonds and amino/cation–π interactions at protein–DNA interfaces was defined as cation–π/H‐bond stair motif (Rooman ., ).
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Further Reading

Banaszak LJ (2000) Foundation of Structural Biology. London, UK: Academic Press.

Branden C and Tooze J (1998) Introduction to Protein Structure, 2nd edn. New York, NY: Garland Publishing.

Travers A and Buckle M (2000) DNA‐Protein Interactions. A Practical Approach. Oxford, UK: Oxford University Press.

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How to Cite close
Rooman, Marianne, and Wintjens, René(Mar 2015) Protein–DNA Interactions. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001348.pub3]