Fig. 3: The architecture of p22 and the NOX2–p22 interface.
a Structure model of p22 (red ribbon, with the C-terminus colored orange) associating with NOX2 (blue surface), viewed parallel to the membrane. Approximate membrane boundaries are indicated in gray and interface lipids are highlighted in green. Hexagon labels refer to zoom-in views shown in panel d. The buried surface area between p22 and NOX2 is ~7400 Å2. b Structure of p22 and NOX2 viewed perpendicular to the membrane. c Close-up view of the p22 core at the intracellular side, highlighting bulkier sidechains that contribute to hydrophobic packing and form polar interactions. The C-terminus of p22 (orange) contacts the p22 core via Trp131. d Close-up view of key interaction sites at the NOX2–p22 interface. Colored hexagon labels indicate the location of each site in panel (a). Top left: on p22 ECL1 residue Thr34 forms a hydrogen bond with NOX2 TM3 residue Glu124. The ECL2 of p22 does not extend outside the membrane and is capped by NOX2, where p22 residue Leu105 contributes to a hydrophobic patch with NOX2. Right: a lipid molecule, represented in green stick with gray mesh, is wedged between p22 and NOX2. Residues at this interface (p22:Ala16, Ile20; NOX2:Trp106, Ala109) form a shape-complementing surface for the bound lipid. Residues Lys195, Arg198, and Arg199 on NOX2 ICL2 create a positively charged patch that may favor a negatively charged phospholipid headgroup. Bottom: residues in the conserved TXXT-motif (Thr191, Ser192, Ser192, Thr194 in NOX2) form hydrogen bonds with sidechains on the N-terminus of p22 (Trp9, Gln13). e Two lipid molecules (green stick with gray mesh) are observed between p22 ECL1 and NOX2 loop A.
