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TitleThe maternal PADI6-UHRF1-UBE2D complex regulates ubiquitination during oocyte maturation and embryogenesis.
Journal, issue, pagesNat Struct Mol Biol, Year 2026
Publish dateMar 2, 2026
AuthorsJinhong Li / Yuechao Lu / Zhili Xia / Pengliang Chi / Qianqian Qi / Sibei Liu / Sicheng Ju / Jialu Li / Zihan Zhang / Zhuo Han / Qingting Liu / Wenbo Meng / Jing Chen / Xiang Wang / Li Guo / Lei Li / Wei Huang / Lunzhi Dai / Junhong Han / Shaorong Gao / Dong Deng /
PubMed AbstractProteostasis in mammalian oocytes is vital for successful reproduction. The cytoplasmic lattices (CPLs) of oocytes store essential maternal proteins for early embryo development. Here we show that ...Proteostasis in mammalian oocytes is vital for successful reproduction. The cytoplasmic lattices (CPLs) of oocytes store essential maternal proteins for early embryo development. Here we show that PADI6, a core component of CPLs, forms a conserved ternary complex that we term MPU for maternal PADI6-UHRF1-UBE2D. The MPU complex regulates protein ubiquitination during oocyte maturation and early embryogenesis. We determined the cryo-electron microscopy structure of MPU and show that 86% (25/29) of clinically identified PADI6 missense variants disrupt MPU assembly, revealing a potential molecular mechanism linking dysregulation of ubiquitination on oocytes to abnormal embryonic development. Mechanistically, PADI6, with the assistance of UHRF1, sequesters UBE2D to prevent ubiquitin transfer from E2 to relevant substrate proteins, thereby suppressing the ubiquitination cascade. Therefore, our findings implicate PADI6 in the regulation of proteostasis by controlling the ubiquitination cascade, expanding our understanding of PADI6-dependent regulation of oocyte maturation and early embryogenesis.
External linksNat Struct Mol Biol / PubMed:41772195
MethodsEM (single particle)
Resolution3.03 Å
Structure data

63270

9lpk

EMDB-63270, PDB-9lpk:
Structure of human PADI6-UHRF1-UBE2D3 complex
Method: EM (single particle) / Resolution: 3.03 Å

Source
  • homo sapiens (human)
KeywordsLIGASE/HYDROLASE / PADI6 / UHRF1 / UBE2D3 / ubiquitylation / maternal complex / early embryonic development / LIGASE-HYDROLASE complex

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