Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Cryo-EM structure of the QseG-QseE complex reveals an accessory protein-driven two-component system activation mechanism.
Journal, issue, pages	mBio, Vol. 16, Issue 12, Page e0286425, Year 2025
Publish date	Dec 10, 2025
Authors	Piqian Gong / Guobang Li / Weixun Li / Mengyuan Xu / Xuyao Jiao / Xudong Chen / Beile Gao / Xiang Gao /
PubMed Abstract	The two-component system (TCS) enables bacteria to sense and respond to environmental changes through histidine kinase-mediated signaling cascades. Although the core components of TCSs have been ...The two-component system (TCS) enables bacteria to sense and respond to environmental changes through histidine kinase-mediated signaling cascades. Although the core components of TCSs have been extensively studied, the molecular basis of accessory proteins in modulating histidine kinase activity remains poorly understood. Here, we report that the outer membrane lipoprotein QseG functions as an accessory protein that directly binds to and activates the histidine kinase QseE via its C-terminal domain. Cryo-electron microscopy (Cryo-EM) structural analysis of the QseG-QseE complex reveals a novel yet conserved interaction mode between an accessory lipoprotein and a histidine kinase, which bridges the outer membrane to cytoplasm. Furthermore, systematic truncation assays and photo-crosslinking experiments indicate that outer membrane-anchored QseG is sufficient and prone to engage with and activate the inner membrane histidine kinase QseE under cultured conditions. Our findings provide mechanistic details for accessory lipoprotein-mediated TCS activation, expanding our understanding of bacterial signaling. The evolutionary conservation of this interaction across bacterial pathogens underscores its broad biological significance and potential as a therapeutic target.IMPORTANCEThe classical TCS system in bacterial signal transduction is composed of two proteins-a histidine kinase and its cognate response regulator. More and more studies have revealed the presence of accessory proteins that can modulate the histidine kinase activity and affect signal transduction, but their mechanisms remain largely elusive. This study unveils a previously unrecognized mechanism by which bacterial accessory lipoproteins mediate TCS activation. We provide compelling evidence that QseG directly interacts with QseE through an evolutionarily conserved structural interface, readily and sufficiently activating QseE's autokinase activity and downstream signaling. Given the essential role of QseEF in bacterial virulence and stress adaptation, our findings pave the way for the development of antimicrobial strategies targeting this conserved lipoprotein-mediated activation mechanism.
External links	mBio / PubMed:41247015 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	2.1 - 3.9 Å
Structure data	63539 9m08 EMDB-63539, PDB-9m08: Structure of outer membrane lipoprotein QseG and histidine kinase QseE complex Method: EM (single particle) / Resolution: 3.9 Å PDB-9m06: Outer membrane lipoprotein QseG of Salmonella enterica serovar Typhimurium SL1344 Method: X-RAY DIFFRACTION / Resolution: 2.1 Å PDB-9m07: Histidine kinase QseE sensor domain of Salmonella Typhimurium SL1344 Method: X-RAY DIFFRACTION / Resolution: 2.4 Å
Chemicals	ChemComp-ACT: ACETATE ION ChemComp-PEG: DI(HYDROXYETHYL)ETHER ChemComp-HOH: WATER
Source	salmonella enterica subsp. enterica serovar typhimurium str. sl1344 (bacteria)
Keywords	SIGNALING PROTEIN / signal activation / Histidine kinase / complex