Transcription Factors

Describe the general characteristics of gene regulatory proteins, including binding sites and interactions made with target DNA

By "gene regulatory protein," I'm going to assume that we mainly have to learn about transcription factors, since transcription is the stage at which most gene regulation takes place.

Transcription factors have two domains: a DNA-binding domain, and an activation or repression domain. The former usually binds to the major groove of DNA, whereas the latter usually binds to other proteins to regulate transcription. Be aware that the bonds to DNA are not via base pairs (since proteins don't have bases that can pair with the DNA)- instead, they bond through hydrogen bonds, ionic bonds, hydrophobic interactions and so forth.

Describe the specific structural components, DNA interactions, and dimerisation ability of helix-turn-helix, zinc finger, leucine zipper, helix-loop-helix, two-stranded beta-sheet, loop region

These few paragraphs are to do with different "motifs," or types of structures, that you might see in regulatory proteins.

Helix-turn-helix: these are, as the name suggests, two alpha helices with a short chain (the "turn") between them. The helices are held at a fixed angle due to the interactions between them. One of the helices, usually the more C-terminal one, is the "recognition helix" that fits into the major groove of the DNA. The other helix (the more N-terminal one) tends to have more structural and positioning roles. Often two transcription factors with the helix-turn-helix motif will bind to the DNA as a dimer. As there are more contacts with the DNA due to the dimerisation, there is an increased binding affinity with the DNA.

Zinc finger: these are "finger-shaped" structures that include at least one Zn2+ ion. They are defined by the residues that associate and coordinate the Zn2+ ion. Common groups are Cys-Cys-His-His (C2H2) or Cys-Cys-Cys-Cys (C4) zinc finger motifs. The Zn2+ ions help to stabilise the "finger" structure. One example of a transcription factor containing the Zn2+ motif is the glucocorticoid receptor (so-called because they thought it was a boring old receptor before they figured out that it was a transcription factor). It contains a C4 zinc finger motif. It can bind glucocorticoid steroid hormones such as cortisol, which are produced during starvation and high physical activity. When bound, it can act as an activator, stimulating the transcription of genes that increase glucose production in the liver.

Leucine zipper: these consist of two alpha-helices that are coiled around each other (the "coiled-coil" structure). Each alpha helix has a hydrophobic leucine residue at every seventh position, allowing for hydrophobic interactions between the helices. The two helices work together as a dimer that contacts two adjacent major grooves.

Helix-loop-helix (HLH): these are somewhat similar to helix-turn-helix in that they consist of two alpha helices, but there are some differences. Firstly, while helix-turn-helix proteins tend to bind to the DNA at their C-terminal helix, the C-terminal helices of helix-loop-helix motifs instead form a coiled-coil structure (HLH motifs can form homodimers or heterodimers). It's the N-terminal helices that contain basic amino acids that interact with the DNA. I'll probably have to find out a bit more about the differences between HLH and helix-turn-helix motifs, as I'm pretty confused at the moment.

Two-stranded beta-sheet: as the name suggests, their binding sites are beta sheets rather than alpha helices. Like other motifs, two-stranded beta-sheets often work in dimers, with each monomer contributing one strand to interact with the major groove of the DNA.

Loop regions: these are simply regions that don't have a defined structure like alpha helices or beta sheets. Some of these regions are also capable of recognising major and/or minor grooves.

Describe combinatorial control involving gene regulatory proteins

Combinatorial control involves the bringing together of different transcription factors. Several different monomers may recognise the same DNA sequence, but the combinations in which they bind may affect transcription. Alternatively, different monomers may recognise the different DNA sequences in a given area. The monomers themselves may be expressed only in particular cells at particular times, allowing for combinatorial control of transcription.