Allostery through DNA drives phenotype switching

Gabriel Rosenblum (), Nadav Elad, Haim Rozenberg, Felix Wiggers, Jakub Jungwirth and Hagen Hofmann ()
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Gabriel Rosenblum: Department of Chemical and Structural Biology
Nadav Elad: Department of Chemical Research Support
Haim Rozenberg: Department of Chemical and Structural Biology
Felix Wiggers: Department of Chemical and Structural Biology
Jakub Jungwirth: Weizmann Institute of Science
Hagen Hofmann: Department of Chemical and Structural Biology

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Allostery is a pervasive principle to regulate protein function. Growing evidence suggests that also DNA is capable of transmitting allosteric signals. Yet, whether and how DNA-mediated allostery plays a regulatory role in gene expression remained unclear. Here, we show that DNA indeed transmits allosteric signals over long distances to boost the binding cooperativity of transcription factors. Phenotype switching in Bacillus subtilis requires an all-or-none promoter binding of multiple ComK proteins. We use single-molecule FRET to demonstrate that ComK-binding at one promoter site increases affinity at a distant site. Cryo-EM structures of the complex between ComK and its promoter demonstrate that this coupling is due to mechanical forces that alter DNA curvature. Modifications of the spacer between sites tune cooperativity and show how to control allostery, which allows a fine-tuning of the dynamic properties of genetic circuits.

Date: 2021
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DOI: 10.1038/s41467-021-23148-2

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