Related Experiment Video

Updated: Dec 9, 2025

Inducible and Reversible Dominant-negative DN Protein Inhibition
08:35

Inducible and Reversible Dominant-negative DN Protein Inhibition

Published on: January 7, 2019

8.6K

Structures of mouse DUOX1-DUOXA1 provide mechanistic insights into enzyme activation and regulation

Ji Sun1

  • 1Department of Structural Biology, St Jude Children's Research Hospital, Memphis, TN, USA. ji.sun@stjude.org.

Nature Structural & Molecular Biology
|September 15, 2020
PubMed

Insights

The study reveals the structure of the DUOX1-DUOXA1 complex, uncovering how NADPH binding activates this enzyme. It also identifies an inactive dimer-of-dimers state, suggesting oligomerization controls DUOX1 activity.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Molecular Mechanisms

Background:

  • DUOX1 (dual oxidase 1) is an NADPH oxidase crucial for thyroid hormone synthesis and host defense.
  • It forms an active complex with its maturation factor, DUOXA1.
  • Mechanisms of DUOX1 activation and regulation are not fully understood.

Purpose of the Study:

  • To elucidate the structural basis of DUOX1-DUOXA1 complex activation and regulation.
  • To provide atomic-level insights into DUOX1 function.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) to determine complex structures.
  • Biochemical analyses to investigate enzyme activity and interactions.

Main Results:

  • Determined cryo-EM structures of mammalian DUOX1-DUOXA1, with and without NADPH.
  • Revealed atomic details of DUOX1-DUOXA1 interaction, a lipid-mediated NADPH-binding site, and the electron transfer pathway.
  • Identified an inactive dimer-of-dimers DUOX1-DUOXA1 configuration, suggesting oligomerization-dependent regulation.

Conclusions:

  • Structural insights into DUOX1-DUOXA1 activation by NADPH.
  • Discovery of a novel, inactive oligomeric state of DUOX1-DUOXA1.
  • Provides a foundation for understanding DUOX1 regulation and function.

More Related Videos

A Non-random Mouse Model for Pharmacological Reactivation of Mecp2 on the Inactive X Chromosome08:27

A Non-random Mouse Model for Pharmacological Reactivation of Mecp2 on the Inactive X Chromosome

Published on: May 22, 2019

6.6K
Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

8.5K

Related Concept Videos

Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.5K
Operon Model01:23

Operon Model

The operon model represents a fundamental mechanism of gene regulation in prokaryotes, enabling coordinated expression of genes involved in related metabolic or functional pathways. Operons consist of structural genes, a promoter, and an operator, with transcription regulated by repressors, activators, and small effector molecules.Structure and Function of OperonsAn operon is a cluster of structural genes transcribed together under the control of a single promoter. The promoter region...
794
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
1.2K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
8.3K
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
8.2K
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

2.8K