6sz5
From Proteopedia
Human calmodulin bound to a peptide of human NADPH oxidase 5
Structural highlights
Disease[CALM2_HUMAN] Catecholaminergic polymorphic ventricular tachycardia;Brugada syndrome;Romano-Ward syndrome. The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM2 are the cause of LQT15. Function[CALM2_HUMAN] Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696).[1] [2] [3] [NOX5_HUMAN] Calcium-dependent NADPH oxidase that generates superoxide. Also functions as a calcium-dependent proton channel and may regulate redox-dependent processes in lymphocytes and spermatozoa. May play a role in cell growth and apoptosis. Isoform v2 and isoform v5 are involved in endothelial generation of reactive oxygen species (ROS), proliferation and angiogenesis and contribute to endothelial response to thrombin.[4] [5] [6] Publication Abstract from PubMedIt 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. On the mechanism of calcium-dependent activation of NADPH oxidase 5 (NOX5).,Millana-Fananas E, Todesca S, Siccorello A, Masino L, Pompach P, Magnani F, Pastore A, Mattevi A FEBS J. 2019 Nov 30. doi: 10.1111/febs.15160. PMID:31785178[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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