We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here. During the move, Proteopedia will be read only for a short time.

6wxu

From Proteopedia

Jump to: navigation, search

CryoEM structure of mouse DUOX1-DUOXA1 complex in the dimer-of-dimer state

Structural highlights

6wxu is a 4 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.7Å
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A2AQ92_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 PubMed

DUOX1, 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

↑ Sun J. Structures of mouse DUOX1-DUOXA1 provide mechanistic insights into enzyme activation and regulation. Nat Struct Mol Biol. 2020 Nov;27(11):1086-1093. PMID:32929281 doi:10.1038/s41594-020-0501-x