The NADPH oxidase of professional phagocytes is a crucial component of the innate immune response due to its fundamental role in the production of reactive oxygen species that act as powerful microbicidal agents. The activity of this multi-protein enzyme is dependent on the regulated assembly of the six enzyme subunits at the membrane where oxygen is reduced to superoxide anions. In the resting state, four of the enzyme subunits are maintained in the cytosol, either through auto-inhibitory interactions or through complex formation with accessory proteins that are not part of the active enzyme complex. Multiple inputs are required to disrupt these inhibitory interactions and allow translocation to the membrane and association with the integral membrane components. Protein interaction modules are key regulators of NADPH oxidase assembly, and the protein–protein interactions mediated via these domains have been the target of numerous studies. Many models have been put forward to describe the intricate network of reversible protein interactions that regulate the activity of this enzyme, but an all-encompassing model has so far been elusive. An important step towards an understanding of the molecular basis of NADPH oxidase assembly and activity has been the recent solution of the three-dimensional structures of some of the oxidase components. We will discuss these structures in the present review and attempt to reconcile some of the conflicting models on the basis of the structural information available.
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Review Article|
March 08 2005
Activation and assembly of the NADPH oxidase: a structural perspective
Yvonne GROEMPING;
Yvonne GROEMPING
*Abteilung Biomolekulare Mechanismen, Max-Planck-Institut für medizinische Forschung, Heidelberg, Germany
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Katrin RITTINGER
Katrin RITTINGER
1
†Division of Protein Structure, National Institute for Medical Research, London, U.K.
1To whom correspondence should be addressed (email katrin.rittinger@nimr.mrc.ac.uk).
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Publisher: Portland Press Ltd
Received:
November 03 2004
Revision Received:
December 02 2004
Accepted:
December 10 2004
Accepted Manuscript online:
December 10 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 386 (3): 401–416.
Article history
Received:
November 03 2004
Revision Received:
December 02 2004
Accepted:
December 10 2004
Accepted Manuscript online:
December 10 2004
Citation
Yvonne GROEMPING, Katrin RITTINGER; Activation and assembly of the NADPH oxidase: a structural perspective. Biochem J 15 March 2005; 386 (3): 401–416. doi: https://doi.org/10.1042/BJ20041835
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