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-Structure paper
Title | Proteolysis and multimerization regulate signaling along the two-component regulatory system AdeRS. |
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Journal, issue, pages | iScience, Vol. 24, Issue 5, Page 102476, Year 2021 |
Publish date | May 21, 2021 |
Authors | Zhenlin Ouyang / Fang Zheng / Li Zhu / Jan Felix / Di Wu / Ke Wu / Irina Gutsche / Yi Wu / Peter M Hwang / Junjun She / Yurong Wen / |
PubMed Abstract | Bacterial two-component regulatory systems are ubiquitous environment-sensing signal transducers involved in pathogenesis and antibiotic resistance. The two-component regulatory system AdeRS is made ...Bacterial two-component regulatory systems are ubiquitous environment-sensing signal transducers involved in pathogenesis and antibiotic resistance. The 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 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 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. |
External links | iScience / PubMed:34113820 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 1.65 - 26.0 Å |
Structure data | EMDB-30929: EMDB-30930: PDB-7cch: PDB-7cci: |
Chemicals | ChemComp-MG: ChemComp-HOH: |
Source |
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Keywords | SIGNALING PROTEIN / Two-Component regulatory system / Acinetobacter baumannii / Histidine Kinase / AdeS / Multidrug resistance / DNA BINDING PROTEIN / Response regulator / AdeR / receiver domain |