7d3f | pdb_00007d3f
Cryo-EM structure of human DUOX1-DUOXA1 in high-calcium state
Structural highlights
FunctionDUOX1_HUMAN Generates hydrogen peroxide which is required for the activity of thyroid peroxidase/TPO and lactoperoxidase/LPO. Plays a role in thyroid hormones synthesis and lactoperoxidase-mediated antimicrobial defense at the surface of mucosa. May have its own peroxidase activity through its N-terminal peroxidase-like domain.[1] [2] Publication Abstract from PubMedDual 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. Structures of human dual oxidase 1 complex in low-calcium and high-calcium states.,Wu JX, Liu R, Song K, Chen L Nat Commun. 2021 Jan 8;12(1):155. doi: 10.1038/s41467-020-20466-9. PMID:33420071[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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