This entry represents the polybasic or autoinhibitory region (PBR/AIR, an arginine/lysine rich region) found after the second SH3 domain in neutrophil cytosol factor 1 (NCF1/p47phox) []. NCF1 is one of the cytosolic regulatory components of NADPH oxidase and consists of a PX domain at the N-terminal, two tandem SH3 domains, a PBR/AIR and a proline-rich region at the C-terminal. In the resting state, the SH3 domains of NCF1 are masked by an intramolecular interaction with the PBR/AIR, which maintains the enzyme in an inactive form [].
NCF1 (also known as NADPH oxidase subunit p47Phox) is one of the cytosolic regulatory components of NADPH oxidase and consists of a PX domain at the N-terminal, two tandem SH3 domains, a polybasic or autoinhibitory region (PBR/AIR, an arginine/lysine rich region) and a proline-rich region at the C-terminal. In the resting state, the SH3 domains of NCF1 are masked by an intramolecular interaction with the PBR/AIR, which maintains the enzyme in an inactive form []. This entry represents the C-terminal domain which contains conserved PxxP motifs that allow binding to SH3 domains, with subsequent activation of the NADPH oxidase, and generation of superoxide, which plays a crucial role in host defence against microbial infection [].
NADPH oxidase is a multisubunit complex that assembles during phagocytosis to generate reactive oxygen species. NCF2 (p67-phox), NCF1 (p47-phox) are required for activation of the phagocyte NADPH oxidase. The activators p67-phox and p47-phox form a ternary complex together with adaptor protein p40-phox, which participates in activation of the phagocyte oxidase by regulating membrane recruitment of p67-phox and p47-phox [, ].A PB1 domain is present in p67-phox. p40-phox associates with p67-phox via binding of the p40-phox PC motif to the p67-phox PB1 domain [].PB1 domain is a modular domain mediating specific protein-protein interactions which play a role in many critical cell processes. A canonical PB1-PB1 interaction, which involves heterodimerization of two PB1 domains, is required for the formation of macromolecular signaling complexes ensuring specificity and fidelity during cellular signaling. The interaction between two PB1 domain depends on the type of PB1. There are three types of PB1 domains: type I which contains an OPCA motif, acidic aminoacid cluster, type II which contains a basic cluster, and type I/II which contains both an OPCA motif and a basic cluster. Interactions of PB1 domains with other protein domains have been described as noncanonical PB1-interactions []. The p67-phox proteins contain a type II PB1 domain.
