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File:Cro protein complex with DNA.png

Cro protein complex with DNA

DNA-binding proteins [1][2][3] are proteins that are composed of DNA-binding domains and thus have a specific or general affinity for either single or double stranded DNA. Sequence-specific DNA-binding proteins generally interact with the major groove of B-DNA, because it exposes more functional groups that identify a base pair. However there are some known narrow-groove DNA-binding ligands such as Netropsin[4], Distamycin, Hoechst 33258, Pentamidine and others [5].

DNA-binding proteins include transcription factors which modulate the process of transcription, various polymerases, nucleases which cleave DNA molecules, and histones which are involved in chromosome packaging in the cell nucleus. DNA-binding proteins can incorporate such domains as the zinc finger, the helix-turn-helix, and the leucine zipper (among many others) that facilitate binding to nucleic acid.

Interaction of DNA with histones (shown in white, top). These proteins' basic amino acids (below left, blue) bind to the acidic phosphate groups on DNA (below right, red).

Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called chromatin. In eukaryotes this structure involves DNA binding to a complex of small basic proteins called histones, while in prokaryotes multiple types of proteins are involved.[6][7] The histones form a disk-shaped complex called a nucleosome, which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones making ionic bonds to the acidic sugar-phosphate backbone of the DNA, and are therefore largely independent of the base sequence.[8] Chemical modifications of these basic amino acid residues include methylation, phosphorylation and acetylation.[9] These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factors and changing the rate of transcription.[10] Other non-specific DNA-binding proteins in chromatin include the high-mobility group proteins, which bind to bent or distorted DNA.[11] These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosomes.[12]

A distinct group of DNA-binding proteins are the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination and DNA repair.[13] These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loops or being degraded by nucleases.

File:Lambda repressor 1LMB.png

The lambda repressor helix-turn-helix transcription factor bound to its DNA target[14]

In contrast, other proteins have evolved to bind to particular DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one particular set of DNA sequences and activates or inhibits the transcription of genes that have these sequences close to their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription.[15] Alternatively, transcription factors can bind enzymes that modify the histones at the promoter; this will change the accessibility of the DNA template to the polymerase.[16]

As these DNA targets can occur throughout an organism's genome, changes in the activity of one type of transcription factor can affect thousands of genes.[17] Consequently, these proteins are often the targets of the signal transduction processes that control responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to "read" the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible.[18]

File:EcoRV 1RVA.png

The restriction enzyme EcoRV (green) in a complex with its substrate DNA[19]

See also[]

  • DNA-binding domain
  • Single-strand binding protein
  • Zinc finger
  • Leucine Zipper
  • bZIP domain
  • Helix-turn-helix
  • Helix-loop-helix
  • HMG-box
  • Lexitropsin
  • Nucleic acid simulations


  1. Andrew Travers, DNA-protein Interactions. Springer, 1993
  2. C.O. Pabo and R.T. Sauer, Protein-DNA recognition. Annu Rev Biochem. 1984. v.53. pp.293-321.
  3. R.E. Dickerson, The DNA helix and how it is read. Sci Am 1983. v.249. pp.94-111.
  4. C. Zimmer and U. Wähnert, Prog. Biophys. Molec. Biol. 1986. v.47. pp.31-112
  5. P.B. Dervan, Design of sequence-specific DNA-binding molecules. Science 1983. v.232. pp.464-471.
  6. Sandman K, Pereira S, Reeve J (1998). Diversity of prokaryotic chromosomal proteins and the origin of the nucleosome. Cell Mol Life Sci 54 (12): 1350–64.
  7. Dame RT (2005). The role of nucleoid-associated proteins in the organization and compaction of bacterial chromatin. Mol. Microbiol. 56 (4): 858–70.
  8. Luger K, Mäder A, Richmond R, Sargent D, Richmond T (1997). Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389 (6648): 251–60.
  9. Jenuwein T, Allis C (2001). Translating the histone code. Science 293 (5532): 1074–80.
  10. Ito T. Nucleosome assembly and remodelling. Curr Top Microbiol Immunol 274: 1–22.
  11. Thomas J (2001). HMG1 and 2: architectural DNA-binding proteins. Biochem Soc Trans 29 (Pt 4): 395–401.
  12. Grosschedl R, Giese K, Pagel J (1994). HMG domain proteins: architectural elements in the assembly of nucleoprotein structures. Trends Genet 10 (3): 94–100.
  13. Iftode C, Daniely Y, Borowiec J (1999). Replication protein A (RPA): the eukaryotic SSB. Crit Rev Biochem Mol Biol 34 (3): 141–80.
  14. Created from PDB 1LMB
  15. Myers L, Kornberg R (2000). Mediator of transcriptional regulation. Annu Rev Biochem 69: 729–49.
  16. Spiegelman B, Heinrich R (2004). Biological control through regulated transcriptional coactivators. Cell 119 (2): 157–67.
  17. Li Z, Van Calcar S, Qu C, Cavenee W, Zhang M, Ren B (2003). A global transcriptional regulatory role for c-Myc in Burkitt's lymphoma cells. Proc Natl Acad Sci USA 100 (14): 8164–9.
  18. Pabo C, Sauer R (1984). Protein-DNA recognition. Annu Rev Biochem 53: 293–321.
  19. Created from PDB 1RVA

External links[]

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