7D3F

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

Summary for 7D3F

• Entry DOI: 10.2210/pdb7d3f/pdb
• EMDB information: 30556
• Descriptor: 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)
• Functional Keywords: duox, duoxa, nox, nadph, fad, haem, electron transport
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 473561.33

Authors

Chen, L.,Wu, J.X. (deposition date: 2020-09-19, release date: 2020-12-09, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (2.6 Å)