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Review
. 2009 Apr 30;41(4):217-25.
doi: 10.3858/emm.2009.41.4.058.

p47phox, the phagocyte NADPH oxidase/NOX2 organizer: structure, phosphorylation and implication in diseases

Jame El-Benna  1 , Pham My-Chan Dang, Marie Anne Gougerot-Pocidalo, Jean Claude Marie, Francoise Braut-Boucher
Affiliations
Review

p47phox, the phagocyte NADPH oxidase/NOX2 organizer: structure, phosphorylation and implication in diseases

Jame El-Benna et al. Exp Mol Med. .

Abstract

Phagocytes such as neutrophils play a vital role in host defense against microbial pathogens. The anti-microbial function of neutrophils is based on the production of superoxide anion (O2 -), which generates other microbicidal reactive oxygen species (ROS) and release of antimicrobial peptides and proteins. The enzyme responsible for O2 - production is called the NADPH oxidase or respiratory burst oxidase. This multicomponent enzyme system is composed of two trans- membrane proteins (p22phox and gp91phox, also called NOX2, which together form the cytochrome b558) and four cytosolic proteins (p47phox, p67phox, p40phox and a GTPase Rac1 or Rac2), which assemble at membrane sites upon cell activation. NADPH oxidase activation in phagocytes can be induced by a large number of soluble and particulate agents. This process is dependent on the phosphorylation of the cytosolic protein p47phox. p47phox is a 390 amino acids protein with several functional domains: one phox homology (PX) domain, two src homology 3 (SH3) domains, an auto-inhibitory region (AIR), a proline rich domain (PRR) and has several phosphorylated sites located between Ser303 and Ser379. In this review, we will describe the structure of p47phox, its phosphorylation and discuss how these events regulate NADPH oxidase activation.

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Figures

Figure 1
Figure 1
Domain structure of p47phox. p47phox is composed of 390 amino acids with one phox homology (PX) domain (amino acids 4-121), two src homology 3 domains (SH3) domains (amino acids 159-214 (SH3A) and amino acids 229-284 (SH3B)), one autoinhibitory region (AIR) (amino acids 292-340) and a proline-rich region (PRR) (amino acids 363-368). The C-terminal region contains several phosphorylated serines (in red).
Figure 2
Figure 2
Phosphorylation of p47phox induces conformational changes and changes domains interactions. In resting state the two p47phox-SH3 domains interact with the C-terminal region AIR to keep the protein in an auto-inhibited state. Upon activation, p47phox is phosphorylated, this phosphorylation induces conformational changes allowing the binding of the cryptic SH3 domains to the proline-rich region (PRR) of p22phox and PX domain to phosphatidylinositol 3,4-biphosphate (PI3,4P), phosphatidic acid (PA) and moesin.
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