Regulation of gene expression by regulatory proteins

The expression of genes is regulated by processes that affect the rates at which gene products are synthesized and degraded. Much of this regulation occurs at the level of transcription initiation,
mediated by regulatory proteins that either repress transcription (negative regulation) or activate transcription (positive regulation) at specific promoters.
Regulatory proteins are DNA-binding proteins that recognize specific DNA sequences; most have
distinct DNA-binding domains. Within these domains, common structural motifs that bind DNA are the helix-turn-helix, zinc finger, and homeodomain.
Helix-Turn-Helix This DNA-binding motif is crucial to the interaction of many bacterial regulatory proteins with DNA, and similar motifs occur in some eukaryotic\ regulatory proteins. The helix-turn-helix motif comprises about 20 amino acids in two short alpha-helical segments, each seven to nine amino acid residues long, separated by a beta turn . This structure generally is not stable by itself; it is simply the reactive portion of a somewhat larger DNA-binding domain. One of
the two alpha-helical segments is called the recognition helix, because it usually contains many of the amino acids that interact with the DNA in a sequence-specific way. This alpha helix is stacked on other segments of the protein structure so that it protrudes from the protein surface. When bound to DNA, the recognition helix is positioned in or nearly in the major groove. The Lac repressor has this DNA-binding motif .
Zinc Finger In a zinc finger, about 30 amino acid residues form an elongated loop held together at the base by a single Zn2 ion, which is coordinated to four of the residues (four Cys, or two Cys and two His). The zinc does not itself interact with DNA; rather, the coordination of zinc with the amino acid residues stabilizes this small structural motif. Several hydrophobic side chains in the core of the structure also lend stability.. Many eukaryotic DNA-binding proteins contain zinc fingers. The interaction of a single zinc finger with DNA is typically weak, and many DNA-binding proteins, like Zif268, have multiple zinc fingers that substantially enhance binding by interacting simultaneously with the DNA. One DNA-binding protein of the frog Xenopus has 37 zinc fingers. There are few known examples of the zinc finger motif in bacterial proteins. The precise manner in which proteins with zinc fingers bind to DNA differs from one protein to the next. Some zinc fingers contain the amino acid residues that  are important in sequence discrimination, whereas others seem to bind DNA nonspecifically (the amino acids required for specificity are located elsewhere in the protein). Zinc fingers can also function as RNA-binding motifs—for example, in certain proteins that bind eukaryotic mRNAs and act as translational repressors.
Homeodomain Another type of DNA-binding domain has been identified in some proteins that function as transcriptional regulators, especially during eukaryotic development. This domain of 60 amino acids—called the homeodomain, because it was discovered in homeotic genes (genes that regulate the development of body patterns)—is highly conserved and has now been identified in proteins from a wide variety of organisms, including humans The DNA-binding segment of the domain is related to the helix-turn-helix motif. The DNA sequence that encodes this domain is known as the homeobox.