The protein that regulates the lac operon in E. coli. The protein is the product of the lac I gene and functions as a molecular switch in response to inducer molecules. A single bacterium contains only 10 to 20 lac repressor molecules. Each is a homotetramer of Mr 154,520. The monomeric subunit has 360 amino acids, and its structure is diagrammed in A, below. It is composed of four functional domains: the head piece (HP), core domains 1 and 2 (CD1 and CD2), and the tail piece (TP). The HP is at the N terminus (NT), and it contains four alpha helices (represented by circles 1–4), which function in DNA binding. Together, the core domains contain 12 beta sheets (represented by squares A–L) sandwiched between nine alpha helices (circles 5–13). The tail piece contains an alpha helix (circle 14) near the C terminus (CT) of the protein. The average alpha helix contains 11 amino acids; the average beta sheet, 4 or 5. As shown in diagram B, the repressor is a V-shaped molecule. Paired dimers make up the arms of the V, but all four chains are bound together at their C termini. The N termini of each dimer bind to different DNA segments. Inducer molecules can bind to the core in the starred regions. The shape change that follows moves the head piece out of the contact with its binding site on the DNA, and the RNA polymerase can now transcribe the structural genes of the operon. See Chronology, 1966, Gilbert and Müller-Hill; 1996, Lewis et al.
(Reprinted with permission from M. Lewis et al., 1996, Crystal structure of the lactose operon repressor and its complexes with DNA and inducer. Science 271 : 1247–1254. © 1996 American Association for the Advancement of Science.)
Subjects: Genetics and Genomics — Chemistry.