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Crystal structure of the λ repressor and a model for pairwise cooperative operator binding

Abstract

Bacteriophage λ has for many years been a model system for understanding mechanisms of gene regulation1. A ‘genetic switch’ enables the phage to transition from lysogenic growth to lytic development when triggered by specific environmental conditions. The key component of the switch is the cI repressor, which binds to two sets of three operator sites on the λ chromosome that are separated by about 2,400 base pairs (bp)2,3. A hallmark of the λ system is the pairwise cooperativity of repressor binding4. In the absence of detailed structural information, it has been difficult to understand fully how repressor molecules establish the cooperativity complex. Here we present the X-ray crystal structure of the intact λ cI repressor dimer bound to a DNA operator site. The structure of the repressor, determined by multiple isomorphous replacement methods, reveals an unusual overall architecture that allows it to adopt a conformation that appears to facilitate pairwise cooperative binding to adjacent operator sites.

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Figure 1: Schematic representations of the dimeric repressor bound to the operator.
Figure 2: Stereo and space-filling views of the dimeric repressor bound to an operator fragment.
Figure 3: λ Repressor binds cooperatively to adjacent operator sites.
Figure 4: Models of the intact repressor octamer reveal the structural basis for alternate pairwise cooperativity.

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Protein Data Bank

Data deposits

Atomic coordinates and structure factor amplitudes have been deposited in the Protein Data Bank under the accession number 3BDN.

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Acknowledgements

We thank S. Garrity for reading this manuscript.

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Correspondence to Mitchell Lewis.

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The file contains Supplementary Table 1 and Supplementary Figures 1-2 with Legends. (PDF 3412 kb)

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Stayrook, S., Jaru-Ampornpan, P., Ni, J. et al. Crystal structure of the λ repressor and a model for pairwise cooperative operator binding. Nature 452, 1022–1025 (2008). https://doi.org/10.1038/nature06831

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