从Sema7A和A39R复合体与PlexinC1的Sema7A和A39R复合体中识别和模仿病毒的结构基础
Heli Liu1, Z Sean Juo, Ann Hye-Ryong Shim
1Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Cell
|August 24, 2010
概括
赛马福林-普莱克辛C1相互作用对于细胞通信至关重要. 结构分析揭示了Semaphorin 7A (Sema7A) 和病毒模仿物 (A39R) 如何结合Plexin C1,为保存的识别机制提供了洞察力.
科学领域:
- 分子和细胞生物学分子和细胞生物学
- 结构生物学 结构生物学
- 免疫学 免疫学 免疫学
背景情况:
- 通过塞马福林和普莱克辛的排斥信号调节神经,免疫和心血管系统.
- 赛马林7A (Sema7A) 在免疫和神经环境中通过Plexin C1.1发挥作用.
- A39R是Sema7A的病毒模仿物,是由天花病毒分泌的.
研究的目的:
- 为了阐明Semahorin-Plexin C1相互作用的结构基础.
- 为了比较Sema7A及其病毒模仿物A39R与Plexin C1.1的结合.
主要方法:
- 使用X射线晶体学来确定Sema7A-Plexin C1和A39R-Plexin C1复合物的结构.
- 结构分析的重点是Plexin C1.1的Semaphorin结合模块.
主要成果:
- 无论是Sema7A还是A39R,都与Plexin C1形成2:2复合体,其中Semaphorin二元体将两个Plexin C1分子连接起来.
- 塞马福林4c-4d循环插入Plexin C1叶片3上的槽,定义了绑定接口.
- A39R通过保留关键的快素结合元素来模仿Sema7A,可能实现更高的亲和力.
结论:
- 这些结构支持一个保存的Semaphorin-Plexin识别模式.
- 普雷克辛激活可能是通过由塞马福林结合诱导的二元化发生的.
- 了解这些相互作用可以为针对细胞信号通路的治疗策略提供信息.
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