Mechanism of CcdA-Mediated Rejuvenation of DNA Gyrase

Aghera, NK and Prabha, J and Tandon, H and Chattopadhyay, G and Vishwanath, S and Srinivasan, N and Varadarajan, R (2020) Mechanism of CcdA-Mediated Rejuvenation of DNA Gyrase. In: Structure, 28 (5). 562-572.e4.

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Abstract

Most biological processes involve formation of transient complexes where binding of a ligand allosterically modulates function. The ccd toxin-antitoxin system is involved in plasmid maintenance and bacterial persistence. The CcdA antitoxin accelerates dissociation of CcdB from its complex with DNA gyrase, binds and neutralizes CcdB, but the mechanistic details are unclear. Using a series of experimental and computational approaches, we demonstrate the formation of transient ternary and quaternary CcdA:CcdB:gyrase complexes and delineate the molecular steps involved in the rejuvenation process. Binding of region 61�72 of CcdA to CcdB induces the vital structural and dynamic changes required to facilitate dissociation from gyrase, region 50�60 enhances the dissociation process through additional allosteric effects, and segment 37�49 prevents gyrase rebinding. This study provides insights into molecular mechanisms responsible for recovery of CcdB-poisoned cells from a persister-like state. Similar methodology can be used to characterize other important transient, macromolecular complexes. © 2020 Elsevier Ltd Aghera et al. elucidate the molecular mechanisms responsible for extraction of the bacterial toxin CcdB from its complex with DNA gyrase, using a combination of experimental FRET kinetic measurements and computational normal mode and perturbation response scanning analyses to identify and characterize the transient molecular complexes involved in the process. © 2020 Elsevier Ltd

Item Type:	Journal Article
Publication:	Structure
Publisher:	Cell Press
Additional Information:	Copy right for this article belongs to Cell Press
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	20 Oct 2020 10:14
Last Modified:	20 Oct 2020 10:14
URI:	http://eprints.iisc.ac.in/id/eprint/65348

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