人类平面细胞极性核蛋白Vangl1的冷EM结构和寡合化
Fan Zhang1, Shaobai Li1, Hao Wu2,3,4
1Shanghai Institute of Precision Medicine, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Nature communications
|January 3, 2025
概括
人类Vangl1蛋白质形成复杂的结构,特别是三元体的二元体. 这种寡合化对于结合Prickle1至关重要,为平面细胞极性信号和相关的发育缺陷 (如神经管缺陷) 提供了洞察力.
科学领域:
- 分子生物学分子生物学
- 发育生物学是发展生物学.
- 结构生物学是结构生物学.
背景情况:
- 旺格尔是平面细胞极性 (PCP) 信号发送中的核心蛋白质,对细胞定向和组织发育至关重要.
- 旺格尔的突变与人类的先天性疾病有关,包括神经管缺陷 (NTD).
- 对Vangl的有限分子表征阻碍了对PCP信号传递和相关疾病的理解.
研究的目的:
- 阐明人类Vangl1寡合化的分子机制.
- 研究Vangl1与PCP效应器Prickle1 (Pk1) 之间的相互作用.
- 提供对Vangl相关人类疾病的分子洞察力.
主要方法:
- 生物化学分析以确定Vangl1的寡合状态.
- 瓦格尔的结构分析1.
- 在体外结合测试以评估Vangl1-Pk1相互作用.
- 将人类疾病相关突变映射到Vangl1结构上.
主要成果:
- 人类Vangl1形成了一个独特的寡合结构:二分体的三分体.
- 在体外,Vangl1三元体的二元化增强了与Prickle1 (Pk1) 的结合.
- 与疾病相关的突变可能会影响Vangl1的脂质结合,中心前庭和寡合化.
结论:
- Vangl1的寡合化是调节其与Prickle1.1相互作用的关键机制.
- 对Vangl1寡合化及其与Pk1相互作用的结构洞察力提升了对PCP信号的理解.
- 这项研究为调查Vangl相关发育障碍提供了分子基础.
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