Fig. 5: CGD mutations in the NOX2 core complex.

Reported missense mutations in p22, NOX2 TMD and NOX2 ECL that lead to chronic granulomatous disease (CGD) are highlighted in green, orange, and pink, respectively. The center panel shows an overall view, with CGD mutations shown as spheres. Side panels provide a close-up view of selected mutations. Sidechains not reported as CGD mutations, but that are part of relevant interactions or the nearby chemical environment are colored light red for p22 and blue for NOX2. a Missense mutations Leu105Arg and Leu120Pro are predicted to disrupt the hydrophobic patch at the p22 ECL-NOX2 interface, and mutation Trp125Cys is expected to disrupt interaction with two lipids found at the interface. b The conserved loop E disulfide bond would be disrupted by mutations Cys244Ser/Arg/Gly/Tyr and Cys257Arg/Ser. Missense mutations Leu45Arg, Leu141Pro, Leu144Pro, and Leu153Arg are predicted to disrupt the hydrophobic packing in the ECLs, and the Tyr41Asp mutation would break an important hydrogen bond that connects loop A and E. c The Glu53Val/Gln, Arg90Trp/Gly/Gln/Pro, His94Arg, and Tyr121His missense mutations are predicted to destabilize the core of p22 and subsequently disrupt NOX2–p22 association. d Missense mutations Thr191Ser and Ser193Pro/Phe in the conserved ¹⁹¹TXXT¹⁹³-motif and Arg198Trp, conserved in NOX1–5 and DUOX1/2, would disrupt important interactions between NOX2 and p22, potentially destabilizing the structural scaffold near the inner heme.