Genetic switching by the Lac repressor is based on two-state Monod–Wyman–Changeux allostery

Romanuka, Julija; Folkers, Gert E.; Gnida, Manuel; Kovačič, Lidija; Wienk, Hans; Kaptein, Robert; Boelens, Rolf

doi:10.1073/pnas.2311240120

Genetic switching by the Lac repressor is based on two-state Monod–Wyman–Changeux allostery

Journal Article · Wed Nov 29 00:00:00 EST 2023 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.2311240120· OSTI ID:2403420

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Utrecht University (Netherlands); Shell Global Solutions International B.V., Amsterdam (Netherlands); SLAC
Utrecht University (Netherlands)
Utrecht University (Netherlands); SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)
Utrecht University (Netherlands); Novartis Pharma, Basel (Switzerland)
Utrecht University (Netherlands); The Netherlands Cancer Institute, Amsterdam (Netherlands)

High-resolution NMR spectroscopy enabled us to characterize allosteric transitions between various functional states of the dimeric Escherichia coli Lac repressor. In the absence of ligands, the dimer exists in a dynamic equilibrium between DNA-bound and inducer-bound conformations. Binding of either effector shifts this equilibrium toward either bound state. Analysis of the ternary complex between repressor, operator DNA, and inducer shows how adding the inducer results in allosteric changes that disrupt the interdomain contacts between the inducer binding and DNA binding domains and how this in turn leads to destabilization of the hinge helices and release of the Lac repressor from the operator. Based on our data, the allosteric mechanism of the induction process is in full agreement with the well-known Monod–Wyman–Changeux model.

View Accepted Manuscript (DOE)

Research Organization:: SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 2403420

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 49 Vol. 120; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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allostery
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Genetic switching by the Lac repressor is based on two-state Monod–Wyman–Changeux allostery

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