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

• DOI: 10.1111/febs.15160
• Publication Date: 2019-12-02T10:26:59Z
• Authors: Elisa Millana Fañ...; Sofia Todesca; Alessandro Sicorello; Laura Masino; Petr Pompach; Francesca Magnani; Annalisa Pastore; Andrea Mattevi
• Keywords: HAMP domain; NOX1

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 played by NADPH oxidases (NOXs), a group seven membrane‐bound enzymes (NOX1‐5 DUOX1‐2) whose unique function to produce ROS. Here, we describe regulation NOX5, widespread family member present cyanobacteria, protists, plants, fungi, animal kingdom. We show calmodulin‐like regulatory EF‐domain NOX5 partially unfolded detached from rest protein absence calcium. In presence calcium, C‐terminal lobe acquires an ordered more compact structure enables its binding enzyme dehydrogenase (DH) domain. Our spectroscopic mutagenesis studies further identified set conserved aspartate residues DH domain essential for activation. Altogether, our work shows calcium induces unfolded‐to‐folded transition promotes direct interaction with region, resulting