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A closer view of the conformation of the Lac repressor bound to operator

Nature Structural Biology volume 7, pages 209–214 (2000)Cite this article

Abstract

Crystal structures of the Lac repressor, with and without isopropylthiogalactoside (IPTG), and the repressor bound to operator have provided a model for how the binding of the inducer reduces the affinity of the repressor for the operator. However, because of the low resolution of the operator-bound structure (4.8 Å), the model for the allosteric transition was presented in terms of structural elements rather than in terms of side chain interactions. Here we have constructed a dimeric Lac repressor and determined its structure at 2.6 Å resolution in complex with a symmetric operator and the anti-inducer orthonitrophenylfucoside (ONPF). The structure enables the induced (IPTG-bound) and repressed (operator-bound) conformations of the repressor to be compared in atomic detail. An extensive network of interactions between the DNA-binding and core domains of the repressor suggests a possible mechanism for the allosteric transition.

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Figure 1: Structure of the dimeric Lac repressor bound to operator and ONPF.
Figure 2: Comparison of the conformations of the Lac repressor bound to operator and inducer.
Figure 3: Interactions of the Lac repressor with operator and ONPF.
Figure 4: Interactions at the dimer interface of the repressor.

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Acknowledgements

We thank G. Van Duyne and P. Lu for useful discussions. This work was supported by an NIH grant to M.L. and an NIH NRSA to C.E.B. The work is based upon research conducted at the NSLS beamline X25 and at the Cornell High Energy Synchrotron Source (CHESS) with the use of the Macromolecular Diffraction at CHESS (MacCHESS) facility.

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  1. The Johnson Foundation and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, 37th and Hamilton walk, Philadelphia, 19102-6059, Pennsylvania, USA

    Charles E. Bell & Mitchell Lewis

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  1. Charles E. Bell
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  2. Mitchell Lewis
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Correspondence to Mitchell Lewis.

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Bell, C., Lewis, M. A closer view of the conformation of the Lac repressor bound to operator . Nat Struct Mol Biol 7, 209–214 (2000). https://doi.org/10.1038/73317

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