DNA-Binding Specificity of Regulatory Proteins

• Eg: CAP, TATA-box binding protein, lac repressor

• Many of these proteins contain a DNA-binding domain which protrudes from the “core” of the protein.

• In most cases, the core contains the allosteric effector site, where the inducer binds.

• Certain protruding α-helices fit into the major groove of the DNA.  In the case of the lac repressor, two α-helices, each from a different monomer interact with two consecutive turns of the major groove of the DNA.

• Note the “helix-turn-helix” structure of the protruding helices, which is a very common motif found in many regulatory proteins.

• The “Zinc-finger” motif is also quite common.  A zinc atom is conjugated with 2 cysteines and 2 histadines of a small part of a polypeptide chain, creating a finger like projection which is able to act with specific DNA sequences.

Cooperative Interactions and DNA-Binding Activity (on main page as new link)

There are often multiple copies of the same type of docking site (transcription factor binding site) near one another on a gene.

 It appears that having several copies of a transcription factor binding to adjacent sites leads to an amplified or superadditive effect of the transcription factors on activating transcription.

It is now thought that this works by the multiple bound sites acting to catalyze the formation of an enhanceosome, a large protein complex that mediates the interactions between distant enhancers and basal transcriptional machinery.