The recent X-ray structure of the PX domain of p47phox, a critical subunit of the NADPH oxidase, unexpectedly revealed the presence of two distinct lipid binding pockets within this single modular domain. This unusual feature allows the p47phox PX domain to integrate signal transduction events emerging from two different lipid signaling pathways.
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Structural profiles of the full phagocyte NADPH oxidase unveiled by combining computational biology and experimental knowledge.
J Biol Chem
December 2024
Institut de Chimie Physique, UMR 8000, CNRS, Université Paris Saclay, Orsay, France. Electronic address:
Article Synopsis
- The phagocyte NADPH oxidase (NOX2) is essential for the innate immune system, producing reactive oxygen species that help destroy pathogens.
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Reynosin protects neuronal cells from microglial neuroinflammation by suppressing NLRP3 inflammasome activation mediated by NADPH oxidase.
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June 2024
Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang 110000, China; National Frontiers Science Center for Industrial Intelligence and Systems Optimization, Key Laboratory of Data Analytics and Optimization for Smart Industry, Ministry of Education, Northeastern University, Shenyang 110000, China. Electronic address:
Neuroinflammation, mediated by the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing-3 (NLRP3) inflammasome, is a significant contributor to the pathogenesis of neurodegenerative diseases (NDDs). Reynosin, a natural sesquiterpene lactone (SL), exhibits a broad spectrum of pharmacological effects, suggesting its potential therapeutic value. However, the effects and mechanism of reynosin on neuroinflammation remain elusive.
View Article and Find Full Text PDFAtox1 regulates macrophage polarization in intestinal inflammation via ROS-NLRP3 inflammasome pathway.
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Biochemistry
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Department of Chemistry, Virginia Commonwealth University, Richmond, Virginia 22384, United States.
As a key component for NADPH oxidase 2 (NOX2) activation, the peripheral membrane protein p47 translocates a cytosolic activating complex to the membrane through its PX domain. This study elucidates a potential regulatory mechanism of p47 recruitment and NOX2 activation by inositol hexaphosphate (IP6). Through NMR, fluorescence polarization, and FRET experimental results, IP6 is shown to be capable of breaking the lipid binding and membrane anchoring events of p47-PX with low micromolar potency.
View Article and Find Full Text PDFThe NADPH oxidase 2 subunit p47 binds to the WAVE regulatory complex and p22 in a mutually exclusive manner.
J Biol Chem
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Roy J. Carver Department of Biochemistry, Biophysics & Molecular Biology, Iowa State University, Ames, Iowa, USA. Electronic address:
The actin cytoskeleton and reactive oxygen species (ROS) both play crucial roles in various cellular processes. Previous research indicated a direct interaction between two key components of these systems: the WAVE1 subunit of the WAVE regulatory complex (WRC), which promotes actin polymerization and the p47 subunit of the NADPH oxidase 2 complex (NOX2), which produces ROS. Here, using carefully characterized recombinant proteins, we find that activated p47 uses its dual Src homology 3 domains to bind to multiple regions within the WAVE1 and Abi2 subunits of the WRC, without altering WRC's activity in promoting Arp2/3-mediated actin polymerization.
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