King's College London

Research portal

On the mechanism of calcium-dependent activation of NADPH oxidase 5 (NOX5): On the mechanism of calcium-dependent activation of NADPH oxidase 5 (NOX5)

Research output: Contribution to journalArticle

Elisa Millana-Fañanas, Sofia Todesca, Alessandro Sicorello, Laura Masino, Francesca Magnani, Annalisa Pastore, Andrea Mattevi

Original languageEnglish
JournalFEBS Journal
Early online date30 Nov 2019
Accepted/In press30 Nov 2019
E-pub ahead of print30 Nov 2019

Documents

  • Revised_Manuscript_FEBS_Elisa20191124

    Revised_Manuscript_FEBS_Elisa20191124.docx, 73.2 KB, application/vnd.openxmlformats-officedocument.wordprocessingml.document

    Uploaded date:09 Dec 2019

    Version:Accepted author manuscript

    Licence:CC BY-NC

King's Authors

Abstract

It is now accepted that Reactive Oxygen Species (ROS) are not only dangerous oxidative agents but also chemical mediators of the redox cell signaling and innate immune response. A central role in ROS controlled production is played by the NADPH oxidases (NOXs), a group of seven membrane-bound enzymes (NOX1-5 and DUOX1-2) whose unique function is to produce ROS. Here, we describe the regulation of NOX5, a widespread family-member present in cyanobacteria, protists, plants, fungi and the animal kingdom. We show that the calmodulin-like regulatory EF-domain of NOX5 is partially unfolded and detached from the rest of the protein in the absence of calcium. In the presence of calcium, the C-terminal lobe of the EF-domain acquires an ordered and more compact structure that enables its binding to the enzyme dehydrogenase domain. Our spectroscopic and mutagenesis studies further identified a set of conserved aspartate residues in the dehydrogenase domain that are essential for NOX5 activation. Altogether, our work shows that calcium induces an unfolded-to-folded transition of the EF-domain that promotes direct interaction with a conserved regulatory region, resulting in NOX5 activation.

Download statistics

No data available

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454