The NADPH oxidase 2 subunit p47phox binds to the WAVE regulatory complex and p22phox in a mutually exclusive manner

• Published in: The Journal of biological chemistry 2024-04, Vol.300 (4), p.107130-107130, Article 107130
• Main Authors: Kuihon, Simon V.N.P., Sevart, Brodrick J., Abbey, Colette A., Bayless, Kayla J., Chen, Baoyu
• Format: Article
• Language: English
• Subjects: actin cytoskeleton; Arp2/3; NADPH oxidase; NOX2; p47phox; ROS; WAVE complex; WRC
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/j.jbc.2024.107130

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 p47phox subunit of the NADPH oxidase 2 complex (NOX2), which produces ROS. Here, using carefully characterized recombinant proteins, we find that activated p47phox 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. Notably, contrary to previous findings, p47phox uses the same binding pocket to interact with both the WRC and the p22phox subunit of NOX2, albeit in a mutually exclusive manner. This observation suggests that when activated, p47phox may separately participate in two distinct processes: assembling into NOX2 to promote ROS production and engaging with WRC to regulate the actin cytoskeleton.