结构生物学 结构生物学. 结构性基础 Notch1 参与类似德尔塔的4
Vincent C Luca1, Kevin M Jude1, Nathan W Pierce2
1Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Science (New York, N.Y.)
|February 21, 2015
概括
划分受体通过Jagd和Delta类 (DLL) 蛋白质控制细胞命运. 在Notch1上进行O链接的糖化是DLL4结合的关键,揭示了糖在细胞信号传递中的化学作用.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 结构生物学 结构生物学
背景情况:
- 划分受体对于哺乳动物细胞命运的决定至关重要.
- 状和三角形状 (DLL) 蛋白质是Notch受体的关键配体.
- 链糖化是一种在Notch蛋白中发现的翻译后修饰.
研究的目的:
- 为了阐明Notch1-DLL4相互作用的结构基础.
- 为了研究Notch1 O-链 glycosylation 在配体结合中的作用.
- 了解翻译后修改如何影响Notch信号.
主要方法:
- 在2.3安格斯特罗姆分辨率下测定Notch1-DLL4复合物的结构的X射线晶体学.
- 分析了Notch1和DLL4.4之间的蛋白质与蛋白质相互作用.
- 糖化Notch1域的生物化学和结构特征.
主要成果:
- 晶体结构显示了Notch1和DLL4之间的两位,反平行结合方向.
- 1表皮生长因子类似的重复11和12与DLL4的DSL和MNNL域相互作用.
- 在Notch1上,O-糖和O-葡萄糖充当替代氨基酸,与DLL4形成重要的接触.
结论:
- 与O结合的甘氨酸在Notch1-DLL4参与中发挥着直接的化学作用.
- 痕信号传导能力与发育调节的糖基化途径有关.
- 这项研究为Notch-ligand相互作用提供了结构和化学基础.
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