8U86

Structural Basis of Human NOX5 Activation

8U86 の概要

• エントリーDOI: 10.2210/pdb8u86/pdb
• EMDBエントリー: 42015
• 分子名称: NADPH oxidase 5, HEME B/C, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (7 entities in total)
• 機能のキーワード: enzyme, oxidase, activation mechanism, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 170464.58

構造登録者

Cui, C.,Jiang, M.,Sun, J. (登録日: 2023-09-15, 公開日: 2024-05-01, 最終更新日: 2024-11-06)

主引用文献

Cui, C.,Jiang, M.,Jain, N.,Das, S.,Lo, Y.H.,Kermani, A.A.,Pipatpolkai, T.,Sun, J.
Structural basis of human NOX5 activation.
Nat Commun, 15:3994-3994, 2024

PubMed Abstract: NADPH oxidase 5 (NOX5) catalyzes the production of superoxide free radicals and regulates physiological processes from sperm motility to cardiac rhythm. Overexpression of NOX5 leads to cancers, diabetes, and cardiovascular diseases. NOX5 is activated by intracellular calcium signaling, but the underlying molecular mechanism of which - in particular, how calcium triggers electron transfer from NADPH to FAD - is still unclear. Here we capture motions of full-length human NOX5 upon calcium binding using single-particle cryogenic electron microscopy (cryo-EM). By combining biochemistry, mutagenesis analyses, and molecular dynamics (MD) simulations, we decode the molecular basis of NOX5 activation and electron transfer. We find that calcium binding to the EF-hand domain increases NADPH dynamics, permitting electron transfer between NADPH and FAD and superoxide production. Our structural findings also uncover a zinc-binding motif that is important for NOX5 stability and enzymatic activity, revealing modulation mechanisms of reactive oxygen species (ROS) production.

PubMed: 38734761
DOI: 10.1038/s41467-024-48467-y

実験手法

ELECTRON MICROSCOPY (3.3 Å)