6wxu
From Proteopedia
CryoEM structure of mouse DUOX1-DUOXA1 complex in the dimer-of-dimer state
Structural highlights
FunctionA2AQ92_MOUSE 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.[ARBA:ARBA00003796] Publication Abstract from PubMedDUOX1, an NADPH oxidase family member, catalyzes the production of hydrogen peroxide. DUOX1 is expressed in various tissues, including the thyroid and respiratory tract, and plays a crucial role in processes such as thyroid hormone biosynthesis and innate host defense. DUOX1 co-assembles with its maturation factor DUOXA1 to form an active enzyme complex. However, the molecular mechanisms for activation and regulation of DUOX1 remain mostly unclear. Here, I present cryo-EM structures of the mammalian DUOX1-DUOXA1 complex, in the absence and presence of substrate NADPH, as well as DUOX1-DUOXA1 in an unexpected dimer-of-dimers configuration. These structures reveal atomic details of the DUOX1-DUOXA1 interaction, a lipid-mediated NADPH-binding pocket and the electron transfer path. Furthermore, biochemical and structural analyses indicate that the dimer-of-dimers configuration represents an inactive state of DUOX1-DUOXA1, suggesting an oligomerization-dependent regulatory mechanism. Together, my work provides structural bases for DUOX1-DUOXA1 activation and regulation. Structures of mouse DUOX1-DUOXA1 provide mechanistic insights into enzyme activation and regulation.,Sun J Nat Struct Mol Biol. 2020 Nov;27(11):1086-1093. doi: 10.1038/s41594-020-0501-x. , Epub 2020 Sep 14. PMID:32929281[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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