Structure of human phagocyte NADPH oxidase in the activated state

Xiaoyu Liu, Yiting Shi, Rui Liu, Kangcheng Song and Lei Chen ()
Additional contact information
Xiaoyu Liu: Peking University, Beijing Key Laboratory of Cardiometabolic Molecular Medicine
Yiting Shi: Peking University, Beijing Key Laboratory of Cardiometabolic Molecular Medicine
Rui Liu: Peking University, Beijing Key Laboratory of Cardiometabolic Molecular Medicine
Kangcheng Song: Peking University, Beijing Key Laboratory of Cardiometabolic Molecular Medicine
Lei Chen: Peking University, Beijing Key Laboratory of Cardiometabolic Molecular Medicine

Nature, 2024, vol. 627, issue 8002, 189-195

Abstract: Abstract Phagocyte NADPH oxidase, a protein complex with a core made up of NOX2 and p22 subunits, is responsible for transferring electrons from intracellular NADPH to extracellular oxygen1. This process generates superoxide anions that are vital for killing pathogens1. The activation of phagocyte NADPH oxidase requires membrane translocation and the binding of several cytosolic factors2. However, the exact mechanism by which cytosolic factors bind to and activate NOX2 is not well understood. Here we present the structure of the human NOX2–p22 complex activated by fragments of three cytosolic factors: p47, p67 and Rac1. The structure reveals that the p67–Rac1 complex clamps onto the dehydrogenase domain of NOX2 and induces its contraction, which stabilizes the binding of NADPH and results in a reduction of the distance between the NADPH-binding domain and the flavin adenine dinucleotide (FAD)-binding domain. Furthermore, the dehydrogenase domain docks onto the bottom of the transmembrane domain of NOX2, which reduces the distance between FAD and the inner haem. These structural rearrangements might facilitate the efficient transfer of electrons between the redox centres in NOX2 and lead to the activation of phagocyte NADPH oxidase.

Date: 2024
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-024-07056-1 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:627:y:2024:i:8002:d:10.1038_s41586-024-07056-1

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-024-07056-1

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().