母亲的PADI6-UHRF1-UBE2D复合体在卵细胞成熟和胚胎发生过程中调节了无处不在
Jinhong Li1, Yuechao Lu1,2, Zhili Xia3
1Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China.
Nature structural & molecular biology
|March 2, 2026
概括
一个新发现的MPU复合体,涉及母亲的PADI6,UHRF1和UBE2D,调节卵细胞中的蛋白质泛化. 大多数PADI6变种破坏了这个复合体,可能导致异常的胚胎发育.
科学领域:
- 生殖生物学 生殖生物学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 卵细胞蛋白质稳定对于生殖成功至关重要.
- 卵细胞中的细胞质晶格 (CPL) 储存对早期胚胎发育至关重要的母体蛋白质.
- PADI6是卵细胞CPL的一个关键组成部分.
研究的目的:
- 研究PADI6在卵细胞成熟和早期胚胎发生中的作用.
- 描述涉及PADI6.6的蛋白质复合体.
- 为了阐明PADI6介导的泛化调节的分子机制.
主要方法:
- 低温电子显微镜以确定MPU复合体的结构.
- 对临床识别的PADI6误解变体的分析.
- 生物化学试验研究蛋白质无化调节.
主要成果:
- 鉴定了一种保存的三元复合体,MPU (母体PADI6-UHRF1-UBE2D),对卵细胞蛋白质稳定至关重要.
- 确定了MPU复合体的冷EM结构.
- 发现86%的临床PADI6变体破坏了MPU组装,将其与异常的胚胎发育联系起来.
- 证明MPU复合体通过隔离UBE2D.来抑制无处不在级联.
结论:
- 通过MPU复合体,PADI6通过控制ubiquitination级联来调节哺乳动物卵细胞中的蛋白质稳定.
- 由于PADI6变体导致的MPU复合组合的失调提供了异常胚胎发育的分子基础.
- 这些发现扩大了对卵细胞成熟和胚胎生成中的PADI6依赖调节的理解.
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