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-Structure paper
タイトル | Structures of mouse DUOX1-DUOXA1 provide mechanistic insights into enzyme activation and regulation. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 27, Issue 11, Page 1086-1093, Year 2020 |
掲載日 | 2020年9月14日 |
![]() | Ji Sun / ![]() |
PubMed 要旨 | 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 ...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. |
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手法 | EM (単粒子) |
解像度 | 2.7 - 3.3 Å |
構造データ | EMDB-21962, PDB-6wxr: EMDB-21963, PDB-6wxu: EMDB-21964, PDB-6wxv: |
化合物 | ![]() ChemComp-FAD: ![]() ChemComp-NAG: ![]() ChemComp-HEM: ![]() ChemComp-HEC: ![]() ChemComp-PX2: ![]() ChemComp-PLC: ![]() ChemComp-HEB: ![]() ChemComp-NDP: ![]() ChemComp-CA: |
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