7U8G

Cryo-EM structure of the core human NADPH oxidase NOX2

7U8G の概要

• エントリーDOI: 10.2210/pdb7u8g/pdb
• EMDBエントリー: 26383
• 分子名称: EGFP, Cytochrome b-245 heavy chain chimera, Cytochrome b-245 light chain, 7G5 - heavy chain, ... (7 entities in total)
• 機能のキーワード: heterodimer, complex, nadph oxidase, enzyme, oxidoreductase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 170000.59

構造登録者

Noreng, S.,Ota, N.,Sun, Y.,Masureel, M.,Payandeh, J.,Yi, T.,Koerber, J.T. (登録日: 2022-03-08, 公開日: 2022-10-26, 最終更新日: 2024-10-16)

主引用文献

Noreng, S.,Ota, N.,Sun, Y.,Ho, H.,Johnson, M.,Arthur, C.P.,Schneider, K.,Lehoux, I.,Davies, C.W.,Mortara, K.,Wong, K.,Seshasayee, D.,Masureel, M.,Payandeh, J.,Yi, T.,Koerber, J.T.
Structure of the core human NADPH oxidase NOX2.
Nat Commun, 13:6079-6079, 2022

PubMed Abstract: NOX2 is the prototypical member of the NADPH oxidase NOX superfamily and produces superoxide (O), a key reactive oxygen species (ROS) that is essential in innate and adaptive immunity. Mutations that lead to deficiency in NOX2 activity correlate with increased susceptibility to bacterial and fungal infections, resulting in chronic granulomatous disease. The core of NOX2 is formed by a heterodimeric transmembrane complex composed of NOX2 (formerly gp91) and p22, but a detailed description of its structural architecture is lacking. Here, we present the structure of the human NOX2 core complex bound to a selective anti-NOX2 antibody fragment. The core complex reveals an intricate extracellular topology of NOX2, a four-transmembrane fold of the p22 subunit, and an extensive transmembrane interface which provides insights into NOX2 assembly and activation. Functional assays uncover an inhibitory activity of the 7G5 antibody mediated by internalization-dependent and internalization-independent mechanisms. Overall, our results provide insights into the NOX2 core complex architecture, disease-causing mutations, and potential avenues for selective NOX2 pharmacological modulation.

PubMed: 36241643
DOI: 10.1038/s41467-022-33711-0

実験手法

ELECTRON MICROSCOPY (3.2 Å)