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

Détails

ID Serval
serval:BIB_9F48DED38483
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Molecular basis of phosphorylation-induced activation of the NADPH oxidase.
Périodique
Cell
Auteur(s)
Groemping Y., Lapouge K., Smerdon S.J., Rittinger K.
ISSN
0092-8674 (Print)
ISSN-L
0092-8674
Statut éditorial
Publié
Date de publication
2003
Volume
113
Numéro
3
Pages
343-355
Langue
anglais
Résumé
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.
Mots-clé
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
Oui
Création de la notice
28/11/2011 16:13
Dernière modification de la notice
08/05/2019 22:51
Données d'usage