Regulatory proteins contain domains not only for DNA binding but also for protein–protein interactions with RNA polymerase, other regulatory proteins or with other subunits of the same regulatory proteins. For examples, they include many eukaryotic transcription factors that function as gene activators. Some important examples of protein–protein interaction domains include the leucine zipper and the helix-loop-helix (HLH) domain.
Leucine Zipper
This domain contains four or five leucine residues spaced at intervals of seven amino acids resulting in their hydrophobic side chains being exposed at one side of a helical region. This region serves as the dimerization domain for two protein subunits, which are held together by hydrophobic interactions between the leucine side chains. Immediately following the leucine zipper is a region that is rich in positively charged amino acid such as lysine and arginine that binds the DNA (Figure 7.15 (c)).
HLH Domain
This is the common structural motif occurring in some eukaryotic regulatory proteins implicated in the control of gene expression during the development of multicellular organisms. These proteins have a conserved region of about 50 amino acids important both for DNA binding as well as for protein dimerization. This region can form short amphipathic α-helices linked by a loop of variable length. The HLH domain of two proteins interacts to form dimers. In these proteins, DNA binding is mediated by a short amino acid sequence that is rich in basic residues (Figure 7.15 (d)).