Lambda repressor
From Proteopedia
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{{STRUCTURE_3bdn| PDB=3bdn | SCENE='Bacteriophage_Lambda_Repressor_cI/Homodimer_bound_to_dna/3'}} | {{STRUCTURE_3bdn| PDB=3bdn | SCENE='Bacteriophage_Lambda_Repressor_cI/Homodimer_bound_to_dna/3'}} | ||
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== Introduction == | == Introduction == | ||
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 (Stayrook et. al 2008). | 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 (Stayrook et. al 2008). | ||
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==C-Terminal Domain (CTD)== | ==C-Terminal Domain (CTD)== | ||
| - | <StructureSection load='3bdn' size='350' side='left' caption='Dimerized CTDs of two | + | <StructureSection load='3bdn' size='350' side='left' caption='Dimerized CTDs of two cI monomers. Note the interactions between knotted β-sheets at the dimer-interface. Auto-cleavage active site residues are colored yellow. (PDB entry [[1F39]])' scene='Bacteriophage_Lambda_Repressor_cI/Ctd_dimer/1'>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 <scene name='Bacteriophage_Lambda_Repressor_cI/Cleavage_site_and_active_site/2'>active site</scene> of the auto-cleavage mechanism of Lambda Repressor is on the CTD. Two amino acid residues mediate the auto-cleavage activity of the repressor, Lys 192 and Ser 149 (Stayrook et. al 2008).</StructureSection> |
Revision as of 08:18, 27 November 2012
Contents |
Introduction
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 (Stayrook et. al 2008).
Structural Overview
The Lambda Repressor is composed of two identical polypeptide chains of 236 amino acid residues. The dimer is formed primarily 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 et. al 2008). 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 (Ndjonka et. al 2006). Four homodimers complex together to form a functional through cooperative-binding. The octamer is formed by interactions between the CTDs of eight monomers. The CTDs of the octamer are shown to the right. Polar (magenta) and nonpolar (grey) residues within the core of the protein are highlighted to show some key interactions between monomers (PDB entry 1KCA). This allows simultaneous repression of promoter regions over 2.4 kb apart on the Lambda genome (Stayrook et. al 2008).
C-Terminal Domain (CTD)
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Connecting Region
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N-Terminal Domain (NTD)
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References
- 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
- Ndjonka D, Bell CE. Structure of a hyper-cleavable monomeric fragment of phage lambda repressor containing the cleavage site region. J Mol Biol. 2006 Sep 22;362(3):479-89. Epub 2006 Jul 15. PMID:16934834 doi:10.1016/j.jmb.2006.07.026
- Bell CE, Lewis M. Crystal structure of the lambda repressor C-terminal domain octamer. J Mol Biol. 2001 Dec 14;314(5):1127-36. PMID:11743728 doi:10.1006/jmbi.2000.5196
- Bell CE, Frescura P, Hochschild A, Lewis M. Crystal structure of the lambda repressor C-terminal domain provides a model for cooperative operator binding. Cell. 2000 Jun 23;101(7):801-11. PMID:10892750
- Beamer LJ, Pabo CO. Refined 1.8 A crystal structure of the lambda repressor-operator complex. J Mol Biol. 1992 Sep 5;227(1):177-96. PMID:1387915
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