In-situ cryo-ET of mouse embryos reveals cytoplasmic lattices contain ubiquitin-charged E2-E3 ligase assemblies.

Cytoplasmic lattices in 6/8-cell mouse embryos are resolved at ~4.7 Å, revealing a ~4.5 MDa repeating unit built from at least fourteen proteins.

• Why it matters: CPLs are essential for mammalian embryonic development and protein homeostasis, yet their molecular organization and function were unclear.
• What they did: Using cryo-focused ion beam milling and cryo-electron tomography, the authors mapped CPL macromolecular complexes, including FBXW-SKP1 and modules containing UBE2D and UHRF1.
• The result: Two CPL structural states were observed: one shows ubiquitin-charged UBE2D with ubiquitin held inactive by PADI6, and the other lacks ubiquitin density, consistent with ubiquitin becoming available for transfer.

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