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Article Dans Une Revue iScience Année : 2021

Proteolysis and multimerization regulate signaling along the two-component regulatory system AdeRS

Résumé

Bacterial two-component regulatory systems are ubiquitous environment-sensing signal transducers involved in pathogenesis and antibiotic resistance. The Acinetobacter baumannii two-component regulatory system AdeRS is made up of a sensor histidine kinase AdeS and a cognate response regulator AdeR, which together reduce repression of the multidrug-resistant efflux pump AdeABC. Herein we demonstrate that an N-terminal intrinsically disordered tail in AdeR is important for the upregulation of adeABC expression, although it greatly increases the susceptibility of AdeR to proteasome-mediated degradation. We also show that AdeS assembles into a hexameric state that is necessary for its full histidine kinase activity, which appears to occur via cis autophosphorylation. Taken together, this study demonstrates new structural mechanisms through which two-component systems can transduce environmental signals to impact gene expression and enlightens new potential antimicrobial approach by targeting two-component regulatory systems.

Dates et versions

hal-03335465 , version 1 (06-09-2021)

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Zhenlin Ouyang, Fang Zheng, Li Zhu, Jan Felix, Di Wu, et al.. Proteolysis and multimerization regulate signaling along the two-component regulatory system AdeRS. iScience, 2021, 24 (5), pp.102476. ⟨10.1016/j.isci.2021.102476⟩. ⟨hal-03335465⟩
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