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Title | Structure of human phagocyte NADPH oxidase in the resting state. |
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Journal, issue, pages | Elife, Vol. 11, Year 2022 |
Publish date | Nov 22, 2022 |
Authors | Rui Liu / Kangcheng Song / Jing-Xiang Wu / Xiao-Peng Geng / Liming Zheng / Xiaoyin Gao / Hailin Peng / Lei Chen / |
PubMed Abstract | 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 that ...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 that participate in pathogen killing. The resting phagocyte oxidase is a heterodimeric complex formed by two transmembrane proteins NOX2 and p22. Despite the physiological importance of this complex, its structure remains elusive. Here, we reported the cryo-EM structure of the functional human NOX2-p22 complex in nanodisc in the resting state. NOX2 shows a canonical 6-TM architecture of NOX and p22 has four transmembrane helices. M3, M4, and M5 of NOX2, and M1 and M4 helices of p22 are involved in the heterodimer formation. Dehydrogenase (DH) domain of NOX2 in the resting state is not optimally docked onto the transmembrane domain, leading to inefficient electron transfer and NADPH binding. Structural analysis suggests that the cytosolic factors might activate the NOX2-p22 complex by stabilizing the DH in a productive docked conformation. |
External links | Elife / PubMed:36413210 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.8 - 3.3 Å |
Structure data | EMDB-34389, PDB-8gz3: EMDB-34390: Consensus map of human phagocyte NADPH oxidase in the resting state EMDB-34620: Focus refined map of the constant regions of Fab heavy chain and light chain and TP1170 of human phagocyte NADPH oxidase in the resting state EMDB-34621: Focus refined map of human phagocyte NADPH oxidase core in the resting state EMDB-34622: Focus refined map of the DH domain of human phagocyte NADPH oxidase in the resting state |
Chemicals | ChemComp-FAD: ChemComp-HEM: ChemComp-NAG: ChemComp-LBN: ChemComp-HOH: |
Source |
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Keywords | OXIDOREDUCTASE / NOX2 / p22 / CYBA / CYBB / TP1170 / NOX |