Lambda repressor

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Revision as of 13:25, 17 March 2013

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Template:STRUCTURE 3bdn

Contents 1 Introduction 2 Structural Overview 3 C-Terminal Domain (CTD) 4 Connecting Region 5 N-Terminal Domain (NTD) 6 3D Structures of lambda repressor 7 References

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)

spinqualitylabelsall models Dimerized CTDs of two monomers. Note interactions between knotted β-sheets at the dimer-interface. Auto-cleavage active site residues are in yellow. (PDB entry 1f39) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image 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 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).

Connecting Region

spinqualitylabelsall models 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) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image 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. The natural structural conformation of the repressor is such that the auto-cleavage active site does not contact the CSR. During bacterial stress response, RecA binds to the repressor which induces a conformational change, bringing the CSR into contact with the auto-cleavage active site residues (Ndjonka et. al, 2006).

N-Terminal Domain (NTD)

spinqualitylabelsall models The spacefill model of the NTD highlights the interactions between the repressor and DNA. (PDB entry 1lmb) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image The NTD Lambda repressor consists of the first 92 amino acid residues of the protein and contains the (Stayrook et. al, 2008) 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 (Beamer and Pabo, 1992). The Helix-Turn-Helix motifs of two dimerized NTDs are illustrated in red to the right.

3D Structures of lambda repressor

Updated on 17-March-2013

1lrp – LR – Enterobacteria phage λ
2hnf, 2ho0 – LR (mutant)
1f39 – LR C terminal
1lmb, 1lli – LR + DNA
3bdn – LR (mutant) + DNA

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