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Structures of human dual oxidase 1 complex in low-calcium and high-calcium states

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  • Jing-Xiang Wu

    (Peking University
    Peking University
    Peking University)

  • Rui Liu

    (Peking University)

  • Kangcheng Song

    (Peking University)

  • Lei Chen

    (Peking University
    Peking University
    Peking University)

Abstract

Dual oxidases (DUOXs) produce hydrogen peroxide by transferring electrons from intracellular NADPH to extracellular oxygen. They are involved in many crucial biological processes and human diseases, especially in thyroid diseases. DUOXs are protein complexes co-assembled from the catalytic DUOX subunits and the auxiliary DUOXA subunits and their activities are regulated by intracellular calcium concentrations. Here, we report the cryo-EM structures of human DUOX1-DUOXA1 complex in both high-calcium and low-calcium states. These structures reveal the DUOX1 complex is a symmetric 2:2 hetero-tetramer stabilized by extensive inter-subunit interactions. Substrate NADPH and cofactor FAD are sandwiched between transmembrane domain and the cytosolic dehydrogenase domain of DUOX. In the presence of calcium ions, intracellular EF-hand modules might enhance the catalytic activity of DUOX by stabilizing the dehydrogenase domain in a conformation that allows electron transfer.

Suggested Citation

  • Jing-Xiang Wu & Rui Liu & Kangcheng Song & Lei Chen, 2021. "Structures of human dual oxidase 1 complex in low-calcium and high-calcium states," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20466-9
    DOI: 10.1038/s41467-020-20466-9
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    Cited by:

    1. Chenxi Cui & Meiqin Jiang & Nikhil Jain & Sourav Das & Yu-Hua Lo & Ali A. Kermani & Tanadet Pipatpolkai & Ji Sun, 2024. "Structural basis of human NOX5 activation," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    2. Anton G. Windfelder & Frank H. H. Müller & Benedict Larney & Michael Hentschel & Anna Christina Böhringer & Christoph-Rüdiger Bredow & Florian H. Leinberger & Marian Kampschulte & Lorenz Maier & Yvett, 2022. "High-throughput screening of caterpillars as a platform to study host–microbe interactions and enteric immunity," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Sigrid Noreng & Naruhisa Ota & Yonglian Sun & Hoangdung Ho & Matthew Johnson & Christopher P. Arthur & Kellen Schneider & Isabelle Lehoux & Christopher W. Davies & Kyle Mortara & Kit Wong & Dhaya Sesh, 2022. "Structure of the core human NADPH oxidase NOX2," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

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