NADPH oxidase 2 (NOX2)–Neutrophil cytosol factor 1 (p47phox) protein-protein interface (NOX2–p47phox PPI)

The NOX2–p47phox protein-protein interface is a critical regulatory junction in the assembly of the active NADPH oxidase 2 (NOX2) enzyme complex. NOX2, primarily expressed in phagocytic cells like neutrophils and macrophages, is responsible for the "respiratory burst," which generates large quantities of reactive oxygen species (ROS) to eliminate invading pathogens [1.1.1, 1.2.2]. The activation of this complex is a multi-step process requiring the translocation of cytosolic subunits, specifically the organizer protein p47phox (Neutrophil cytosol factor 1), to the membrane-bound catalytic core consisting of NOX2 (gp91phox) and p22phox [1.2.2, 1.4.1]. The physical interaction between p47phox and NOX2 is essential for the enzyme to adopt its catalytically active conformation [1.3.1, 1.5.1]. Pathological overactivation of this interface leads to excessive ROS production, which is a major driver of oxidative stress in conditions such as hypertension, atherosclerosis, stroke, and neurodegenerative diseases [1.2.2, 1.4.1, 1.5.2]. Therapeutic strategies targeting this interface, such as the peptide inhibitor gp91ds-tat, aim to selectively inhibit NOX2-derived ROS without affecting other NOX isoforms [1.3.1, 1.5.1]. However, because NOX2 is vital for innate immunity, a primary safety concern is the potential for immunosuppression and increased infection risk, similar to the phenotype observed in Chronic Granulomatous Disease [1.1.1, 1.5.1].

Other names

gp91phox–p47phox interfaceCYBB–NCF1 interfaceNADPH oxidase assembly interfacep47phox–p22phox interface

Inhibition of the assembly of the active NADPH oxidase 2 complex by competitively blocking the interaction between the cytosolic organizer subunit p47phox and the membrane-bound catalytic subunit NOX2 (gp91phox) or its partner p22phox.