形复杂结构涉及调整连接体灵敏度的捕获键
Vincent C Luca1,2, Byoung Choul Kim3,4, Chenghao Ge5
1Departments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
概括
切口受体的激活依赖于机械力和糖化. 新的结构数据揭示了 Jagged1 与 Notch1 的结合如何利用这些力量来调节细胞命运的决定.
科学领域:
- 细胞生物学
- 结构生物学
- 生物化学
背景情况:
- 痕信号对于细胞命运的决定至关重要.
- 这种途径依赖于机械力量和蛋白质糖化是独特的.
- 了解分子相互作用是解读诺奇通路调节的关键.
研究的目的:
- 阐明Notch1和Jagged1 (Jag1) 相互作用的结构基础.
- 研究机械力和糖化在Notch1-Jag1结合中的作用.
- 为了比较Notch1与Jag1的结合与Delta-like 4 (DLL4) 连接体.
主要方法:
- 在2.5安格斯特罗姆分辨率的X射线晶体.
- 蛋白质与蛋白质结合界面的分析.
- 蛋白质糖化修饰的特征 (O结合的糖).
主要成果:
- 确定了Notch1-Jag1细胞外复合体的详细结构.
- 在Notch1 EGF域8和12上的O结合与Jag1 EGF3和C2域相互作用.
- 在机械力量的影响下,Jag1在Notch1结合时表现出捕获键行为.
- 与DLL4结合相比,Notch1使用不同的 Jag1 结合域.
结论:
- 机械力和特定的糖化模式对Notch1-Jag1相互作用至关重要.
- Jag1的捕捉键行为允许依赖力调节痕信号.
- 这提供了通过机械线索对联体区分和Notch信号的强化机制.
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