Transcription Factors

Gene-specific factors must position themselves on specific DNA sequences to exert their effects, and the relatively simple structure of DNA offers only a few ways for proteins to grab on. Therefore, despite the wealth of different individual transcription factors, each employs one of only a handful of structural "motifs" to bind to the DNA double helix. Each motif is a small portion of a much larger protein, whose other portions confer DNA-sequence specificity and control its interaction with the basal factors or other proteins.

The helix-turn-helix motif is composed of a short section of alpha-helix, linked to a loop of amino acids that changes the direction of the chain, followed by another alpha-helix. The first helix fits into the so-called major groove of the DNA double helix. The side chains of the protein's amino acids make contact with the exposed portions of the nucleotides. The shape and charges of the one complement those of the other, allowing them to bind; this provides the sequence-specificity needed for effective gene regulation. The homeotic proteins are a special class of proteins employing a modified helix-turn-helix motif. These proteins play critical roles in regulating development in organisms as diverse as fruit flies and humans.

The zinc-finger motif is constructed around an atom of zinc, which binds four amino acids to hold the amino acid chain in proper orientation. While many of the other amino acids vary among different types of zinc-finger proteins, the four key amino acids—either four cysteines or two cysteines and two histidines—are invariant in this class of transcription factors. This group of factors includes the steroid receptors. Steroids are a class of hormones, including testosterone and the estrogen, that exert profound effects on development. Steroids must bind to a receptor to form the transcription factor complex. Mutations in steroid receptors are responsible for a large variety of inherited disorders, including androgen insensitivity syndrome, thyroid hormone resistance syndrome, and some forms of prostate cancer, breast cancer, and osteoporosis.