RT Journal Article
SR Electronic
T1 Structure of human phagocyte NADPH oxidase in the resting state
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.10.04.510768
DO 10.1101/2022.10.04.510768
A1 Liu, Rui
A1 Song, Kangcheng
A1 Wu, Jing-Xiang
A1 Geng, Xiao-Peng
A1 Zheng, Liming
A1 Gao, Xiaoyin
A1 Peng, Hailin
A1 Chen, Lei
YR 2022
UL http://biorxiv.org/content/early/2022/10/04/2022.10.04.510768.abstract
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.