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

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

Groemping Y, Lapouge K, Smerdon SJ, Rittinger K.

Source

Division of Protein Structure, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.

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.

PMID:: 12732142; [PubMed - indexed for MEDLINE]

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Structures reported by this article

Structure Of The P22phox-P47phox Complex

PDB: 1OV3

Source: Homo sapiens, synthetic construct

Method: X-Ray Diffraction

Resolution: 1.8 Å

See all 2 structures...

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

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