Molecular basis of phosphorylation-induced activation of the NADPH oxidase.
Details
Serval ID
serval:BIB_9F48DED38483
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Molecular basis of phosphorylation-induced activation of the NADPH oxidase.
Journal
Cell
ISSN
0092-8674 (Print)
ISSN-L
0092-8674
Publication state
Published
Issued date
2003
Volume
113
Number
3
Pages
343-355
Language
english
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.
Keywords
Amino Acid Sequence, Binding Sites, Cloning, Molecular, Crystallography, X-Ray, Enzyme Activation, Gene Expression Regulation, Humans, Macromolecular Substances, Membrane Transport Proteins, Models, Molecular, Molecular Sequence Data, NADPH Dehydrogenase/chemistry, NADPH Dehydrogenase/metabolism, NADPH Oxidase/antagonists & inhibitors, NADPH Oxidase/chemistry, Phosphoproteins/antagonists & inhibitors, Phosphoproteins/chemistry, Phosphorylation, Protein Binding, Sequence Homology, Amino Acid, Structure-Activity Relationship, Substrate Specificity, src Homology Domains
Pubmed
Web of science
Open Access
Yes
Create date
28/11/2011 16:13
Last modification date
20/08/2019 16:05
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