When an Intramolecular Disulfide Bridge Governs the Interaction of DUOX2 with Its Partner DUOXA2

Antioxidants & Redox Signaling
Aurore CarréCorinne Dupuy

Abstract

The dual oxidase 2 (DUOX2) protein belongs to the NADPH oxidase (NOX) family. As H2O2 generator, it plays a key role in both thyroid hormone biosynthesis and innate immunity. DUOX2 forms with its maturation factor, DUOX activator 2 (DUOXA2), a stable complex at the cell surface that is crucial for the H2O2-generating activity, but the nature of their interaction is unknown. The contribution of some cysteine residues located in the N-terminal ectodomain of DUOX2 in a surface protein-protein interaction is suggested. We have investigated the involvement of different cysteine residues in the formation of covalent bonds that could be of critical importance for the function of the complex. We report the identification and the characterization of an intramolecular disulfide bond between cys-124 of the N-terminal ectodomain and cys-1162 of an extracellular loop of DUOX2, which has important functional implications in both export and activity of DUOX2. This intramolecular bridge provides structural support for the formation of interdisulfide bridges between the N-terminal domain of DUOX2 and the two extracellular loops of its partner, DUOXA2. Both stability and function of the maturation factor, DUOXA2, are dependent on the oxidative f...Continue Reading

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Citations

Jul 27, 2015·Redox Biology·Sharon O'NeillUlla G Knaus
May 14, 2016·Nature Reviews. Endocrinology·Rabii Ameziane-El-HassaniCorinne Dupuy
Feb 7, 2018·British Journal of Pharmacology·Albert van der VlietDavid E Heppner
Jan 8, 2019·Endocrine-related Cancer·Rabii Ameziane El HassaniCorinne Dupuy
Nov 3, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Karamatullah DanyalAlbert van der Vliet
Jun 3, 2018·The Journal of Microbiology·Demba SarrBalázs Rada
Jul 2, 2017·The Journal of Clinical Endocrinology and Metabolism·Marina M L KizysRui M B Maciel
May 27, 2020·Genetics and Molecular Biology·Caroline Coelho de Faria, Rodrigo Soares Fortunato
Nov 22, 2019·Molecular and Cellular Endocrinology·Héctor M TargovnikCarina M Rivolta
Mar 12, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Nuha Milad AshtiwiBalázs Rada
Apr 4, 2021·Antioxidants·Jessica BouviereRuy A Louzada

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Methods Mentioned

BETA
electrophoresis
transfection
flow cytometry
confocal microscopy
coimmunoprecipitation
immunoprecipitation
protein folding
Fluorescence

Software Mentioned

Spectrum Mill MS Proteomics Workbench

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