Lambda repressor

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IntroductionIntroduction

cI is a transcription inhibitor of bacteriophage Lambda. Also known as Lambda Repressor, cI is responsible for maintaining the lysogenic life cycle of phage Lambda. This is achieved when two repressor dimers bind cooperatively to adjacent operator sites on the DNA. The cooperative binding induces repression of the cro gene and simultaneous activation of the cI gene, which code for proteins Cro and cI, respectively.

Structural OverviewStructural Overview

The Lambda Repressor dimer is composed of two identical polypeptide chains of 236 amino acid residues each. The dimer is formed mainly by interactions between the CTDs, while the NTDs interact weakly in comparison. Each chain is composed of two structurally distinct domains which are connected by a short polypeptide chain which contains a cleavage-sensitive region (CSR). The NTD is responsible for the DNA-binding character of the protein and the CTD is integral in dimerization of the chains, cooperative-binding repression, and the auto-cleavage mechanism (). The principal purpose of the CSR is to provide a region which is both susceptible and insusceptible to cleavage depending upon the conformation the dimer assumes. In addition, the CSR serves to stabilize interactions between chains in the dimer.

C-Terminal Domain (CTD)C-Terminal Domain (CTD)

The CTD of Lambda Repressor assumes a structural conformation similar to a knotted β-sheet and is composed of 104 amino acid resides (residues 132-236). This conformation is key in establishing the dimer-forming interaction with the CTD of the opposite chain. The CTD also facilitates the dimer-dimer interaction necessary for cooperative-binding repression. The active site of the auto-cleavage mechanism of Lambda Repressor is on the CTD. Two amino acid residues mediate the auto-cleavage activity of the repressor, Lys192 and Ser149 ().

spinqualitylabelsall models The auto-cleavage active site on the CTD is highlighted in yellow (residues 149, 192). (PDB entry 3bdn) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

spinqualitylabelsall models The CTD of Lambda Repressor chain A is highlighted in magenta (residues 132-236)(PDB entry 3bdn) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Connecting RegionConnecting Region

The region connecting the NTD to the CTD consists of 38 amino acid residues (residues 93-131) and contains the CSR. The CSR is a long loop (residues 106-126) and serves to stabilize the dimer through interactions with the CSR of the opposite chain. Cleavage occurs between Ala111 and Gly 112 in the CSR.

spinqualitylabelsall models The cleavage site of the connecting region is highlighted in red (residues 111-112), while the auto-cleavage active site of the CTD is highlighted in yellow(residues 149, 192). (PDB entry 3bdn) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

N-Terminal Domain (NTD)N-Terminal Domain (NTD)

The NTD Lambda repressor consists of the first 92 amino acid residues of the protein and contains the DNA-Binding Domain ( DBD) of the protein. The secondary structure of the NTD is a compact conformation of six alpha-helices. This secondary structure shows weak self-association, which is purported to aid in formation of the dimeric unit. The DNA-binding motif utilized by Lambda Repressor is a Helix-Turn-Helix.

spinqualitylabelsall models The NTD of Lambda Repressor is highlighted in green (residues 1-92). The bound DNA strand is highlited in brown. (PDB entry 3bdn) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image