在EGF受体的结构和膜相互作用
Anton Arkhipov1, Yibing Shan, Rahul Das
1D. E. Shaw Research, New York, NY 10036, USA.
Cell
|February 5, 2013
概括
表皮生长因子受体 (EGFR) 使用微妙的机制来控制细胞生长. 膜相互作用决定了EGFR是否形成活跃或非活跃的二次体,调节细胞通路.
科学领域:
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
- 生物物理学的生物物理.
背景情况:
- 表皮生长因子受体 (EGFR) 的激活对于细胞增殖,迁移和分化至关重要.
- 非活性EGFR存在于单体和双体形式,表明复杂的调节机制.
- 细胞膜在EGFR调节中的作用很难从结构上研究.
研究的目的:
- 研究EGFR激活和非激活的结构机制.
- 阐明细胞膜在EGFR二分化和信号传递中的作用.
- 了解细胞外联体结合如何影响EGFR的构造和活性.
主要方法:
- 嵌入膜的EGFR的分子动力学模拟.
- 分析细胞外域,跨膜螺旋和激酶域的构造变化.
- 研究EGFR与细胞膜之间的静电相互作用.
主要成果:
- 结合体的EGFR二分体有利于N端的跨膜螺旋二分化,柔膜片段二分化和不对称的激酶二分体形成 (活性状态).
- 无干EGFR二极体有利于C端的跨膜螺旋二极化,柔膜片段解离,以及对称的激酶二极体形成 (无活性状态).
- 与膜的静电相互作用对于将细胞外事件与细胞内EGFR活动相合至关重要.
结论:
- EGFR激活是一种由细胞外联体结合调节的二元化驱动的过程.
- 细胞膜在通过静电相互作用调节EGFR构成和活性方面发挥着至关重要的作用.
- 了解这些机制,可以了解控制细胞增殖,迁移和分化的细胞通路.
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