The cytoplasmic lattice in mammalian eggs sequesters ubiquitination machinery and tubulin in reserve.

The cytoplasmic lattice (CPL) in mammalian eggs is essential for early embryonic development, but its molecular components, structural organization, and functional capacity have remained elusive. Here, using cryo-electron microscopy, we show that the CPL filament in mouse eggs contains repeating units with a periodicity of ~37 nm, and determine its high-resolution, native structure and complete subunit composition. The CPL architecture organizes maternal-effect proteins, ubiquitination machinery, and tubulin into a highly structured reservoir. Maternal-effect proteins form the scaffold of the CPL to sequester a UBE2D-UHRF1 E2-E3 ubiquitination module and three distinct FBXW E3 ubiquitin ligases, notably all in activity-excluded states. The CPL further contains an αβ-tubulin heterodimer in a GTP-bound state with a calcium ion coordinated to α-tubulin, suggesting microtubule assembly-competent tubulin held in reserve. The CPL structure is capped at each end by a terminal unit that lacks a PADI6 dimer, a scaffold component, thereby preventing further oligomerization. Interactions between maternal-effect proteins in adjacent CPL units promote the assembly of a three-dimensional lattice in the egg cytoplasm. Taken together, our work defines how CPL assembly and architecture prime mammalian eggs for ubiquitin-mediated protein degradation and cytoskeletal remodeling during the egg-to-embryo transition.