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

iScience

Junjun She¹  Peter M. Hwang²  Irina Gutsche³  Jan Felix³  Li Zhu⁴  Di Wu⁴  Ke Wu⁴  Zhenlin Ouyang⁵  Yurong Wen⁵  Fang Zheng⁶  Yi Wu⁶ 

[1] Dentistry, University of Alberta, Edmonton, Alberta T6G 2R3, Canada;;Departments of Medicine and Biochemistry, Faculty of Medicine &Institut de Biologie Structurale, Univ. Grenoble Alpes, CEA, CNRS, IBS, 71 avenue des Martyrs, Grenoble F-38044, France;MOE Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, China;Talent Highland and Center for Gut Microbiome Research of Med-X Institute, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China;The Key Laboratory of Environment and Genes Related to Disease of Ministry of Education, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China;

关键词: Molecular Structure;    Microbiology;    Protein structure aspects;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: 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.

【 授权许可】

Unknown