Molecular basis of phosphorylation-induced activation of the NADPH oxidase.

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Citation

Groemping Y, Lapouge K, Smerdon SJ, Rittinger K

Molecular basis of phosphorylation-induced activation of the NADPH oxidase.

Cell. 2003 May 2;113(3):343-55.

PubMed ID
12732142 [ View in PubMed
]
Abstract

The multi-subunit NADPH oxidase complex plays a crucial role in host defense against microbial infection through the production of reactive oxygen species. Activation of the NADPH oxidase requires the targeting of a cytoplasmic p40-p47-p67(phox) complex to the membrane bound heterodimeric p22-gp91(phox) flavocytochrome. This interaction is prevented in the resting state due to an auto-inhibited conformation of p47(phox). The X-ray structure of the auto-inhibited form of p47(phox) reveals that tandem SH3 domains function together to maintain the cytoplasmic complex in an inactive form. Further structural and biochemical data show that phosphorylation of p47(phox) activates a molecular switch that relieves the inhibitory intramolecular interaction. This permits p47(phox) to interact with the cytoplasmic tail of p22(phox) and initiate formation of the active, membrane bound enzyme complex.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Neutrophil cytosol factor 1P14598Details