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标题：Proteolysis and multimerization regulate signaling along the two-component regulatory system AdeRS
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作者：Zhenlin Ouyang ; Fang Zheng ; Li Zhu 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：5
页码：1-13
DOI：10.1016/j.isci.2021.102476
语种：English
出版社：Elsevier
摘要：SummaryBacterial two-component regulatory systems are ubiquitous environment-sensing signal transducers involved in pathogenesis and antibiotic resistance. TheAcinetobacter baumanniitwo-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 ofadeABCexpression, 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 viacisautophosphorylation. 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.Graphical abstractDisplay OmittedHighlights•Crystal structure of AdeR dimer with traceable N-terminal intrinsically disordered region.•N-terminal intrinsically disordered region AdeR is involved in proteasome proteolysis.•Crystal structure of AdeS catalytic domain demonstratescisautophosphorylation.•AdeS can assemble into hexamer and is crucial for its full kinase activity.Molecular Structure ; Microbiology; Protein structure aspects