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机器人激活和自动抑制的结构原理
Reut Barak1, Galit Yom-Tov1, Julia Guez-Haddad1
1The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Israel.
Cell
|March 12, 2019
概括
圆形 (Robo) 接收器
科学领域:
- 神经科学
- 分子生物学
- 结构生物学
背景情况:
- 神经元的发育依赖于精确的细胞指导.
- 圆形 (Robo) 受体家族和Slit配体调解了这一过程.
- 机器人受体的精确激活机制在很大程度上是未知的.
研究的目的:
- 解释机器人受体激活的分子机制.
- 确定机器人受体自抑制和激活的结构基础.
主要方法:
- 人类Robo2域的X射线晶体.
- 在小鼠初级神经元和C. elegans中进行功能测试.
- 在物种间保存的机器人二元化分析.
主要成果:
- 确定了完整的人类Robo2ectodomain的3.6 Å晶体结构.
- 通过D4域进行的Robo cis二元化是保存的,对功能至关重要.
- 确定了两个自抑制机制: cis 阻断和 trans 相互作用.
- 裂口刺激似乎释放了这种自我抑制,使二分化和激活成为可能.
结论:
- 这项研究揭示了机器人受体的自抑制机制.
- 这种机制涉及 cis 和 trans 相互作用,防止过早激活.
- 裂结合可能会触发自身抑制的释放,导致受体激活和下游信号.
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