Lac repressor

What is the lac repressor?What is the lac repressor?

Repressors are proteins that inhibit the expression of genes; that is, they inhibit the transcription of messenger RNA from their target genes. Each repressor targets a specific co-regulated group of genes by recognizing a specific sequence of DNA, called the operator in bacteria. Repressor proteins are coded for by regulatory genes.

The lactose ("lac") repressor controls the expression of bacterial enzymes involved in the metabolism of of the sugar lactose. When the lac repressor binds lactose, it changes to an inactive conformation that cannot repress the production of these enzymes. Thus, the enzymes needed to use lactose are made only when lactose is available. The lac repressor, and the group of genes it controls, which is called an operon, were the first such gene regulatory system to be discovered. The operon was described in 1960 by François Jacob et al., who also correctly proposed the general mechanism of regulation by the lac repressor. The 1965 Nobel Prize in Physiology or Medicine was awarded to François Jacob, André Lwoff, and Jacques Monod "for their discoveries concerning genetic control of enzyme and virus synthesis".

For a general introduction to the lac repressor, please see David Goodsell's Introduction to the lac repressor in his series Molecule of the Month, and the article in Wikipedia on the lac repressor. Mitchell Lewis published a detailed review in 2005.

Structure of the lac repressorStructure of the lac repressor

spinqualitylabelsall models PDB ID 1lbg Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

The lac repressor protein ( showing chain A in 1lbg, resolution 4.8 Å), starting at the N-terminus, begins with a DNA-binding "headpiece", followed by a hinge region, then an N-terminal ligand-binding subdomain and a C-terminal ligand binding subdomain, a linker, and a C-terminal tetramerization helix. In the absence of DNA, the hinge region does not form the alpha helix shown here.

As can be seen when the chain is

N

C

each of the ligand-binding subdomains is made up of two discontinuous segments.

The lac repressor forms . Dimerization buries 2,200 Ų of surface, including a ,

Hydrophobic, Polar

forming a hydrophobic core (shown with 1lbi, resolution 2.7 Å, where the DNA-binding domain is disordered).

The most highly is the surface that contacts DNA. (Only alpha carbon atoms are shown here, without sidechains, because sidechains were not resolved in the 4.8 Å 1lbg model.) The dimerization surfaces are the of the ligand-binding domains. (This scene shows sidechains, using the 2.7 Å model in 1lbi, which lacks the DNA-binding domain due to disorder.)

The C-terminal tetramerization helices tether two dimers, and thus the functional form of with four DNA-binding sites.

DNA Binding: Bending the OperatorDNA Binding: Bending the Operator

	spinqualitylabelsall models PDB ID 1osl_19_1l1m_9_morph.pdb Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
	Morph of the lac repressor bending DNA as binding changes from non-specific 1osl to specific recognition of the operator sequence 1l1m.

Lac repressor binds to DNA non-specifically, enabling it to slide rapidly along the DNA double helix until it encounters the lac operator sequence. Upon recognizing the specific operator sequence, the binding converts from non-specific to specific. During this conversion, the hinge region goes from a disordered loop to an alpha helix, which binds in the minor groove of the DNA. This binding opens the minor groove, bending the DNA.

.... forming sequence-specific hydrogen bonds with DNA bases.

To Be Continued .... Eric Martz 23:52, 14 October 2008 (IST)