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

0522047 - BTÚ 2020 RIV GB eng J - Článek v odborném periodiku
Fananas, E. M. - Todesca, S. - Sicorello, A. - Masino, L. - Pompach, Petr - Magnani, F. - Pastore, A. - Mattevi, A.
On the mechanism of calcium-dependent activation of NADPH oxidase 5 (NOX5).
FEBS Journal. -, DEC 2019 (2019). ISSN 1742-464X. E-ISSN 1742-4658
Grant CEP: GA MŠMT(CZ) LM2015043
Institucionální podpora: RVO:86652036
Klíčová slova: REACTIVE OXYGEN * CONFORMATIONAL-CHANGES * TERMINAL DOMAIN
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 4.392, rok: 2019
Způsob publikování: Open access
https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.15160

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 (DH) domain. Our spectroscopic and mutagenesis studies further identified a set of conserved aspartate residues in the DH 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.
Trvalý link: http://hdl.handle.net/11104/0306561