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Atomic Interactions between Proteins and DNA

Proteins bind to DNA through the same forces that hold strands of DNA together, namely H-bonds and ionic interactions.

Different amino acids contain H-bond donors and acceptors, and charged residues on their side chains.

DNA binding proteins tend to bind in the major groove of DNA for two reasons.  

First, there is more room for the protein to access the sides of the bases.

Second, the pattern of H-bond donors and acceptors on the bases are more distinct on the major groove of DNA than on the minor groove.  For example, a protein could not tell the difference between an A=T and a T=A base pair in a protein if it bound to the minor groove. 

(Red arrows indicate H-bond acceptors and Green arrows H-bond donors)

DNA binding motifs

DNA binding proteins adopt a set of common three-dimensional structures called motifs.  Within these three dimensional motifs different proteins will have different specific amino acids that will recognize specific H-bond donor and acceptor sites on DNA.  In this way different DNA binding proteins can recognize very specific DNA sequences.

Examples of the most common motifs are shown below.

Estrogen Receptor Binding DNA

Zn finger GCN4 Pho4

Zn6 Cys6 Zinc Cluster: From Gal4,  a regulator of galactose metabolism in some yeast and fungi. Helix-Turn-Helix:  From cAMP Receptor Protein, a regulator of the E. coli lac operon. Practice Exercise Zinc Finger:  From Zif 268, a protein expressed early in mouse development. Leucine Zipper:  bZip transcription factor PAP1 (1gd2) from Schizosaccharomyces pombe   Helix-Loop-Helix: Phosphate System Positive Regulatory Protein Pho4 in yeast.