7D3F

Cryo-EM structure of human DUOX1-DUOXA1 in high-calcium state

7D3F の概要

• エントリーDOI: 10.2210/pdb7d3f/pdb
• EMDBエントリー: 30556
• 分子名称: Dual oxidase 1, Isoform 2 of Dual oxidase maturation factor 1, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (10 entities in total)
• 機能のキーワード: duox, duoxa, nox, nadph, fad, haem, electron transport
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 473561.33

構造登録者

Chen, L.,Wu, J.X. (登録日: 2020-09-19, 公開日: 2020-12-09, 最終更新日: 2024-10-23)

主引用文献

Wu, J.X.,Liu, R.,Song, K.,Chen, L.
Structures of human dual oxidase 1 complex in low-calcium and high-calcium states.
Nat Commun, 12:155-155, 2021

PubMed 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.

PubMed: 33420071
DOI: 10.1038/s41467-020-20466-9

実験手法

ELECTRON MICROSCOPY (2.6 Å)