Subjects

- Cryoelectron microscopy

- Intermediate filaments

- Oogenesis

- Reproductive biology

Abstract

Mammalian oocytes are filled by fibric structure called cytoplasmic lattice (CPL), essential for oocyte maturation and early embryonic development1-3. CPL comprises subcortical maternal complex (SCMC) and multiple components, including PADI62,4,5. 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.

Access through your institution

Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Access Nature and 54 other Nature Portfolio journals

Get Nature+, our best-value online-access subscription

$32.99 / 30 days

cancel any time

Learn more

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Learn more

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Author information

Author notes- These authors contributed equally: Shuxian Liu, Yusong Liu, Junchao Xue, Zhenzhen Li, Yan Zhang

Authors and Affiliations

- College of Life Sciences, Zhejiang University, Hangzhou, China

Shuxian Liu & Bailun Li

- 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

Shuxian Liu, Yusong Liu, Junchao Xue, Zhenzhen Li, Yan Zhang, Bailun Li, Lidan Xu, Zhenzhen Yu, Hongtao Yu, Haishan Gao & En-Zhi Shen

- School of Life Sciences, Fudan University, Shanghai, China

Yusong Liu

- 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

Yusong Liu & Haishan Gao

- State Key Laboratory of Gene Expression, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China

En-Zhi Shen

- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China

Lili Li

Authors- Shuxian LiuView author publications