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-Structure paper
タイトル | Structures of human dual oxidase 1 complex in low-calcium and high-calcium states. |
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ジャーナル・号・ページ | Nat Commun, Vol. 12, Issue 1, Page 155, Year 2021 |
掲載日 | 2021年1月8日 |
著者 | Jing-Xiang Wu / Rui Liu / Kangcheng Song / Lei Chen / |
PubMed 要旨 | 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, ...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. |
リンク | Nat Commun / PubMed:33420071 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.6 - 2.8 Å |
構造データ | EMDB-30555, PDB-7d3e: EMDB-30556, PDB-7d3f: |
化合物 | ChemComp-HEM: ChemComp-NDP: ChemComp-FAD: ChemComp-NAG: ChemComp-NA: ChemComp-HOH: ChemComp-CA: |
由来 |
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キーワード | ELECTRON TRANSPORT / DUOX / DUOXA / NOX / NADPH / FAD / Haem |