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Abstract：
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.
摘要：
肌动蛋白细胞骨架和活性氧（ROS）在各种细胞过程中起着至关重要的作用。先前的研究表明，这些系统的两个关键组件之间存在直接相互作用：WAVE1亚基的WAVE1调节复合物（WRC），促进肌动蛋白聚合，和NADPH氧化酶2复合物（NOX2）的p47phox亚基，产生ROS。这里,使用精心表征的重组蛋白，我们发现激活的p47phox使用其双重SH3结构域与WRC的WAVE1和Abi2亚基内的多个区域结合，而不改变WRC促进Arp2/3介导的肌动蛋白聚合的活性。值得注意的是,与之前的发现相反,p47phox使用相同的结合袋与WRC和NOX2的p22phox亚基相互作用,尽管是以相互排斥的方式。这一观察表明，当被激活时，p47phox可以分别参与两个不同的过程:组装成NOX2以促进ROS产生和与WRC接合以调节肌动蛋白细胞骨架。
