Molecular basis of oocyte cytoplasmic lattice assembly

Nature ( 2026 ) Cite this article
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Mammalian oocytes are filled by fibric structure called cytoplasmic lattice (CPL), essential for oocyte maturation and early embryonic development 1-3 .

CPL comprises subcortical maternal complex (SCMC) and multiple components, including PADI6 2,4,5 .

Despite its discovery in the 1960s, the molecular architecture and assembly mechanisms of CPL have remained poorly understood.

Here we present the cryo-electron microscopy (cryo-EM) structure of the CPL isolated from mouse oocytes.

Our analysis identified 14 constitutive protein subunits and revealed that CPL is composed of repeating “U-shaped basket” (UB) and “adapter ring” (AR)- featured units, forming a filamentous architecture.

AR adopts a two-fold symmetric conformation, containing two NLRP4f, four SCMC and two ZBED3 subunits circularized via two distinct interaction clusters.

The UB is anchored by PADI6, a didecamer composed of ten homodimers assembled by two back-to-back pentamers, each forming the lateral side of UB.

The underfoot base and up-down sides of the UB are formed by multiple central-symmetric assemblies (UBE2D3-UHRF1-NLRP14) and (TUBB2B-TUBB2A-FBXW24-SKP1) respectively, associating with the PADI6 pentamers to construct the intact UB structure.

Two SCMC dimer within each AR connect the up and down sides of two adjacent UBs with an extensive protein-protein interaction network and thus maintain the repetitive connection between the neighboring CPL units.

Our work unveils the architectural principles underlying the assembly of this large, periodic CPL filament, offering a molecular basis for understanding CPL’s functions in early mammalian embryogenesis and female reproductive disorders.

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These authors contributed equally: Shuxian Liu, Yusong Liu, Junchao Xue, Zhenzhen Li, Yan Zhang
College of Life Sciences, Zhejiang University, Hangzhou, China
Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China
Shuxian Liu, Junchao Xue, Zhenzhen Li, Yan Zhang, Lidan Xu & En-Zhi Shen
Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China
Shuxian Liu, Yusong Liu, Junchao Xue, Zhenzhen Li, Yan Zhang, Bailun Li, Lidan Xu, Zhenzhen Yu, Hongtao Yu, Haishan Gao & En-Zhi Shen
Institute of Biology, Westlake Institute for Advanced Study, Hangzhou, China
School of Life Sciences, Fudan University, Shanghai, China
New Cornerstone Science Laboratory, School of Life Sciences, Westlake University, Hangzhou, China
Yusong Liu, Hongtao Yu & Haishan Gao
Zhejiang Key Laboratory of Structural Biology, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
State Key Laboratory of Gene Expression, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
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Correspondence to Haishan Gao or En-Zhi Shen .

Supplementary Information (download PDF )
This file contains Supplementary Figs.

1–5.

Reporting Summary (download PDF )
Supplementary Table 1 (download XLSX )
Proteins identified in the purified CPL by mass spectrometry.

Peer Review File (download PDF )
Supplementary Video 1 (download MP4 )
cryo-EM density map and the assigned atomic model of one UB and two ARs of the CPL.

Supplementary Video 2 (download MP4 )
Detailed display of CPL density map with one UB and two Ars.

Supplementary Video 3 (download MP4 )
Supplementary Video 4 (download MP4 )
Centrosymmetric organization of the UB formed by PADI6.

Supplementary Video 5 (download MP4 )
Dynamic view of the crystal packing of a previously reported structure of PADI6 (PDB 8ql0).

Supplementary Video 6 (download MP4 )
Fitted filament model aligns well with individual filaments within the Cryo-ET-derived CPL framework.

Supplementary Video 7 (download MP4 )
Detailed inspection of the integrated cryo-ET and cryo-EM model reveals specific inter-filament interfaces.

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DOI : https://doi.org/10.1038/s41586-026-10360-7