Structure of DNA

Protein Binding to DNA

Structure of DNA

DNA (deoxyribonucleic acid) consists of 4 different bases two of which are Purines (Adenine and Guanine) and two that are Pyrimidines (Thymine and Cytosine). DNA exists in both single stranded (ss) and double stranded (ds) forms but this paper shall only refer to ds forms. dsDNA can form many different structures. The most commonly cited structure consists of two anti-parallel sugar-phosphate backbones forming a right handed helix; the bases from one strand pointing roughly towards the center of the helix forming a pair with the base on the opposing strand. The bases are restricted in their pairing, Adenine Thymine and Guanine Cytosine. Two important properties of helical dsDNA are the major / minor grooves and the extent of helical turn or twist.

The two main ds helical forms of DNA are that of A-DNA and B-DNA.

Helical DNA structures are by no means a ridged forming supercoiled structures, interactions with proteins and other molecules that result in most 'native' DNA being bent in some way.

Protein binding to DNA

Protein recognition of DNA sequence motifs is thought to be a combination of the protein having affinity for DNA with a certain topology (local conformation and configuration) and its ability to form specific H-bonds with the bases in the sequence.

Restriction enzymes differ from gene regulatory proteins being much more fastidious in their substrate choice (a single base pair change eliminates recognition by the protein) and having shorter recognition sequences (4-8 bp vs. 14-20 bp) with strict dyad symmetries. With molecules such as histones or E.coli trp repressor (regulatory proteins) local conformation and configuration of DNA appears to be the only form of recognition.

As noted in the first section DNA can exist in various conformations which would affect its local topology thus either enhance or limit protein recognition. Regulation occurs at the protein level and also at that of DNA conformation. For example if the site of interaction was in the major groove, protein access to the A-DNA would be severely limited compared to if the DNA was in the B form.

Proteins appear to have a diverse but limited number of motifs that are used in interactions with DNA. These involve both -helices and -sheet secondary structures and are summarized on the next page.

For the sake of comprehension if is easier to think of DNA and protein in a static form but it is important to remember they can adopt many conformations, especially on interaction with other molecules.