Question

Explain how the major and minor grooves in DNA are involved in binding of enzymes and other proteins.

Answer 1

The major and minor groove arise due to the orientation of the base pairs across the helix. The grooves separate the two sugar-phosphate backbones from each other and the atoms exposed in the grooves are accessible to the solvent and to interactions with proteins.

The enegetics profiles of a significant number of protein-DNA systems at 20°C reveal that, despite of the comparable Gibbs free energies, association with the major groove is primarily an enthalpy driven process. Certain proteins bind to DNA to alter its structure or to regulate transcription or replication. It is easier for these DNA binding proteins to interact with bases which are the internal part of the DNA molecule on the major groove side as the backbones are not in the way. Whereas binding to the minor groove is characterised by the unfavourable enthalpy that is compensated by favourable entropic contributions.

The alpha - helix is the most frequently used secondary structure element for specific DNA recognition in the major groove. The positioning of the helix in the major groove can vary between different protein families and also among different proteins with the same family .

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