Lambda repressor
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 is composed of two identical polypeptide chains of 236 amino acid residues each. The dimer is formed mainly by interactions between the C-Terminal domains (CTDs) of two monomers, while the N-Terminal domains (NTDs) interact weakly in comparison. Each monomer is composed of two structurally distinct domains which are connected by a short polypeptide chain containing a cleavage-sensitive region (CSR). The NTD is responsible for the DNA-binding character of the protein; in contrast, the CTD is integral in formation of the functional homodimer, cooperative-binding repression, and the auto-cleavage mechanism (Stayrook). 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 (2HNF). Four homodimers complex together to form a functional through cooperative-binding. This allows simultaneous repression of multiple non-adjacent promoter regions on the Lambda genome (1KCA).
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 homodimer-forming interaction with the CTD of the opposite monomer. 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 (Stayrook). Connecting Region<StructureSection load='3bdn' size='350' side='right' caption='The CSR, consisting of two residues (Ala 111 and Gly 112), is highlighted in red. Cleavage occurs at the peptide bond between these residues. (PDB entry 2HNF)' scene='Bacteriophage_Lambda_Repressor_cI/Csr/1'>The region connecting the NTD to the CTD consists of 38 amino acid residues (residues 93-131) and contains the CSR. The CSR is on a long loop (residues 106-126) which serves to stabilize the homodimer through interactions with the connecting region of the opposite monomer. Cleavage occurs between Ala 111 and Gly 112 in the CSR. | ||||||||||
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.
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ReferenceReference
- ↑ Stayrook S, Jaru-Ampornpan P, Ni J, Hochschild A, Lewis M. Crystal structure of the lambda repressor and a model for pairwise cooperative operator binding. Nature. 2008 Apr 24;452(7190):1022-5. PMID:18432246 doi:10.1038/nature06831