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TitleProteolysis and multimerization regulate signaling along the two-component regulatory system AdeRS.
Journal, issue, pagesiScience, Vol. 24, Issue 5, Page 102476, Year 2021
Publish dateMay 21, 2021
AuthorsZhenlin Ouyang / Fang Zheng / Li Zhu / Jan Felix / Di Wu / Ke Wu / Irina Gutsche / Yi Wu / Peter M Hwang / Junjun She / Yurong Wen /
PubMed AbstractBacterial 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 linksiScience / PubMed:34113820 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.65 - 26.0 Å
Structure data

EMDB-30929:
The negatively stained reconstruction of cytoplasmic AdeS in APO state
Method: EM (single particle) / Resolution: 26.0 Å

EMDB-30930:
The negatively stained reconstruction of cytoplasmic AdeS in ATP-bound state
Method: EM (single particle) / Resolution: 22.0 Å

PDB-7cch:
Acinetobacter baumannii histidine kinase AdeS
Method: X-RAY DIFFRACTION / Resolution: 2.848 Å

PDB-7cci:
Acinetobacter baumannii response regulator AdeR with disordered N terminus
Method: X-RAY DIFFRACTION / Resolution: 1.65 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-HOH:
WATER

Source
  • acinetobacter baumannii (bacteria)
KeywordsSIGNALING PROTEIN / Two-Component regulatory system / Acinetobacter baumannii / Histidine Kinase / AdeS / Multidrug resistance / DNA BINDING PROTEIN / Response regulator / AdeR / receiver domain

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