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卵母细胞细胞质晶格组装的分子基础
作者:小柯机器人 发布时间:2026/3/18 15:20:06

近日,西湖大学申恩志及其课题组开发出卵母细胞细胞质晶格组装的分子基础。这一研究成果发表在2026年3月17日出版的国际学术期刊《自然》上。

在这里,研究组展示了从单母卵母细胞分离的CPL的冷冻电镜(cryo-EM)结构。他们的分析确定了14个组成蛋白亚基,并揭示CPL由重复的“U形篮子”(UB)和“适配器环”(AR)特征单位组成,形成丝状结构。AR采用双重对称构象,包含两个NLRP4f及其SCMC和两个ZBED3亚基,它们通过两个不同的相互作用原子循环。UB由PADI6锚定,PADI6是一个由十个同型二聚体组成的二聚体,由两个背靠背的五聚体组装,每个五聚体形成UB的侧面。UB的足下基部和上下两侧分别由多个中心对称组合(UBE2D3-UHRF1-NLRP14)和(TUBB2B-TUBB2A-FBXW24-SKP1)组成,与PADI6五聚体结合,构成完整的UB结构。每个AR中的两个SCMC二聚体通过广泛的蛋白质-蛋白质相互作用网络连接两个相邻UBs的上下两侧,并保持相邻CPL单元之间的重复连接。他们的工作揭示了这种大型周期性CPL纤维的结构原理,为理解CPL在早期哺乳动物胚胎发生和女性生殖障碍中的功能提供了分子基础。

据悉,哺乳动物卵母细胞充满了称为细胞质晶格(CPL)的纤维结构,这对卵母细胞成熟和早期胚胎发育至关重要。CPL由皮质下母体复合物(SCMC)和多种成分组成,包括PADI6。尽管在20世纪60年代发现了CPL,但人们对其分子结构和组装机制仍然知之甚少。

附:英文原文

Title: Molecular basis of oocyte cytoplasmic lattice assembly

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

Issue&Volume: 2026-03-17

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.

DOI: 10.1038/s41586-026-10360-7

Source: https://www.nature.com/articles/s41586-026-10360-7

期刊信息

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html