6SZ5

Human calmodulin bound to a peptide of human NADPH oxidase 5

Summary for 6SZ5

• Entry DOI: 10.2210/pdb6sz5/pdb
• Descriptor: Calmodulin-2, NADPH oxidase 5, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: nox5, calmodulin, oxidoreductase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 181250.84

Authors

Millana, E.,Mattevi, A. (deposition date: 2019-10-02, release date: 2019-12-11, Last modification date: 2024-01-24)

Primary citation

Millana Fananas, E.,Todesca, S.,Sicorello, A.,Masino, L.,Pompach, P.,Magnani, F.,Pastore, A.,Mattevi, A.
On the mechanism of calcium-dependent activation of NADPH oxidase 5 (NOX5).
Febs J., 287:2486-2503, 2020

PubMed 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 (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.

PubMed: 31785178
DOI: 10.1111/febs.15160

Experimental method

X-RAY DIFFRACTION (2.23 Å)