核孔复合物的细胞质环的结构通过整合性冷-EM和AlphaFold
Pietro Fontana1,2, Ying Dong1,2, Xiong Pi1,2
1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Science (New York, N.Y.)
|June 9, 2022
概括
研究人员使用冷电子显微镜和AlphaFold构建核孔复合体 (NPC) 细胞质环的原子模型. 这为真核细胞的结构和功能提供了新的见解.
科学领域:
- 结构生物学
- 细胞生物学
- 生物化学
背景情况:
- 核毛孔复合体 (NPC) 是一个大型分子机器,在真核细胞中调节细胞核和细胞质之间的运输.
- NPC对于细胞过程至关重要, 它们的功能障碍与人类疾病有关.
- 之前对NPC组织和动态的理解仍然不完整.
研究的目的:
- 在结构上描述 Xenopus laevis 卵细胞 NPC 细胞质环 (CR).
- 使用集成式冷电子显微镜 (cryo-EM) 和AlphaFold结构预测构建CR的原子模型.
- 阐明核波林,特别是Nup358在CR稳定性和NPC生物发生中的作用.
主要方法:
- 对Xenopus laevis卵细胞NPC进行单颗粒冷EM分析.
- 在高分辨率的三维重建CR.
- 核结构和复杂构成的AlphaFold预测.
- 通过将预测结构嵌入到冷电磁密度图中来构建整合模型.
主要成果:
- 在6.9/6.7 Å分辨率重建了Xenopus laevis NPC CR地图.
- 创建了一个几乎完整的CR原子模型,识别了Nup358,Nup214-Nup88-Nup62等关键核素成分.
- 预测Nup358结构揭示了参与CR稳定和FG重复凝结的货物通道的领域.
- AlphaFold预测Nup358具有状卷轴结构,这表明它在NPC组装中的作用.
结论:
- 整合式冷EM和AlphaFold提供了一个强大的方法来建模大型蛋白质复合体.
- 详细的CR模型增强了对NPC分子相互作用和架构的理解.
- 这些发现提升了NPC功能,生物发生和调节的知识,对人类疾病有影响.
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