Question

What types of proteins bind to HTH motifs? Please provide an example or two.

Answer 1

Ans: Mostly DNA binding proteins that regulate gene expression binds to HTH motifs. This motifs provide a sequence specific binding sites for proteins. The HTH or helix-turn-helix motif consists of 20 residues approximately and is characterised by the presence of two alpha-helices, which forms a contact with the DNA wherein they are joined by a short turn.

The first alpha helix has been studied to stabilise the structure whereas the second alpha helix of the motif binds to DNA through hydrophobic interactions and a number of hydrogen bonds which occurs between the exposed bases and specific side chains and thymine methyl groups within the major groove present on the DNA. The HTH of the DNA binding domain contains those residues that is essential for DNA binding.

For example: lac repressor and lamda repressor. Both these proteins have been studied to contain HTH motifs by which it specifically binds to their operators. And lac repressor is nothing but a DNA binding protein that inhibits the gene expression during transcription in the absence of lactose. When lactose is present it binds to the lac repressor and converts it into allolactose ( isomer of lactose) and prevents it from binding the operator region of lac operon thereby allowing the transcription to occur. The lac operon operates this gene expression through the HTH motif present in its DNA binding domain where it binds the bases specifically in the major groove region of the lac operon operator.