Protein Motifs for DNA Binding


Protein–deoxyribonucleic acid (DNA) interactions play a central role in directing the flow of genetic information and in the control of life itself. Research has demonstrated that many DNA‐binding proteins belong to distinct families containing common structural motifs. In this article, several important motifs are introduced and their interactions with DNA are discussed. Interestingly, these motifs show great variability in their DNA‐binding modes. In some cases, a simple structural element, such as a single α helix or β ribbon, accounts for the most critical interactions, whereas in other protein–DNA complexes, more complicated structural scaffolds are required. In addition, the efficiency and specificity of protein–DNA interactions depend on the nature of bonding, the induced fit of macromolecules and the oligomerisation of protein motifs.

Key Concepts:

  • DNA‐binding motifs are prototypic structural elements, each representing a group of DNA‐binding proteins.

  • The stability of protein–DNA complexes is attributed to both sequence‐specific and nonsequence‐specific interactions, whereas the specificity only depends on the former.

  • Conformational change is often observed in protein–DNA complexes, which facilitates the complex formation and/or the following biological function.

  • In addition to promoting extreme conformational change in DNA, oligomerisation of DNA‐binding proteins may also enable regulation of protein–DNA complexes.

Keywords: DNA binding; protein motif; helix–turn–helix; zinc finger; leucine zipper; helix–loop–helix; ribbon–helix–helix; OB fold; histone fold

Figure 1.

DNA‐binding motifs using helices. (a) Helix–turn–helix (HTH) motif, (b) HTH–DNA complex, (c) homeodomain, (d) homeodomain–DNA complex, (e) a single zinc finger (Zn, grey), (f) three consecutive zinc fingers bound to DNA, (g) leucine zipper, (h) helix–loop–helix (HLH) monomer, (i) HLH dimer–DNA complex, (j) HLH‐bZIP–DNA complex. The structures in Figure , Figure and Figure were prepared by the program Swiss PDB Viewer (http://spdbv.vital‐

Figure 2.

DNA‐binding motifs using ribbons. (a) Ribbon–helix–helix (RHH)–DNA complex and (b) integration host factor (IHF)–DNA complex.

Figure 3.

Other DNA‐binding motifs. (a) E. colisingle‐stranded DNA‐binding protein (SSB) monomer; (b) E. coliSSB dimer, showing the extended β sheet; (c) E. coliSSB tetramer; (d) TATA‐binding protein (TBP)–DNA complex; (e) AT hook motif–DNA complex; (f) histone fold; (g) histone fold pair–DNA complex; (h) nucleosome core particle (DNA backbones, blue); (i) ‘wing–helix’ motif (histone H5 globular domain).


Further Reading

Bewley C, Gronenborn A and Clore GM (1998) Minor groove‐binding architectural proteins: structure, function, and DNA recognition. Annual Review of Biophysics and Biomolecular Structure 27: 105–131.

Billeter M (1996) Homeodomain‐type DNA recognition. Progress in Biophysics and Molecular Biology 66: 211–225.

Branden C and Tooze J (1991) Introduction to Protein Structure. New York: Garland.

Kohn W, Mant C and Hodges R (1997) α‐Helical protein assembly motifs. Journal of Biological Chemistry 272: 2583–2586.

Luger K, Mader A, Richmond R, Sargent D and Richmond T (1997) Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 389: 251–260.

Schreiter E and Drennan C (2007) Ribbon–helix–helix transcription factors: variations on a theme. Nature Reviews Microbiology 5: 710–720.

Sera T (2009) Zinc‐finger‐based artificial transcription factors and their applications. Advanced Drug Delivery Reviews 61: 513–526.

Theobald D, Mitton‐Fry R and Wuttke D (2003) Nucleic acid recognition by OB‐fold proteins. Annual Review of Biophysics and Biomolecular Structure 32: 115–133.

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How to Cite close
Xu, Hang, and Morrical, Scott W(Jun 2010) Protein Motifs for DNA Binding. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0002711.pub2]