PT  - JOURNAL ARTICLE
AU  - Liu, Rui
AU  - Song, Kangcheng
AU  - Wu, Jing-Xiang
AU  - Geng, Xiao-Peng
AU  - Zheng, Liming
AU  - Gao, Xiaoyin
AU  - Peng, Hailin
AU  - Chen, Lei
TI  - Structure of human phagocyte NADPH oxidase in the resting state
AID  - 10.1101/2022.10.04.510768
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.10.04.510768
4099  - http://biorxiv.org/content/early/2022/10/04/2022.10.04.510768.short
4100  - http://biorxiv.org/content/early/2022/10/04/2022.10.04.510768.full
AB  - Phagocyte oxidase plays an essential role in the first line of host defense against pathogens. It oxidizes intracellular NADPH to reduce extracellular oxygen to produce superoxide anions for pathogen killing. The resting phagocyte oxidase is a heterodimeric complex formed by two transmembrane proteins NOX2 and p22. Despite the functional importance of this complex, its structure remains elusive. Here we reported the cryo-EM structure of the human NOX2-p22 complex in nanodisc in the resting state. The structure shows that p22 is formed by four transmembrane helices and interacts with NOX2 through its M1 and M4 helices. Hydrophobic residues on M3, M4, and M5 of NOX2 contribute to the complex formation. Structural analysis suggests that the cytosolic factors activate the NOX2-p22 complex by stabilizing the dehydrogenase domain (DH) in a productive docked conformation which is efficient for electron transfer between DH and the transmembrane domain.Competing Interest StatementThe authors have declared no competing interest.