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Ligand Nano-cluster Arrays in a Supported Lipid Bilayer
Published on: April 23, 2017
阿尔法LI域的结构及其与ICAM-1的复合体揭示了整合素调节的形状变化途径
Motomu Shimaoka1, Tsan Xiao1, Jin-Huan Liu2
1The Center for Blood Research, Department of Pathology, Department of Anesthesia, Department of Pediatrics, Boston, Massachusetts 02115.
Cell
|January 16, 2003
概括
与ICAM-1结合的整合素αLβ2I域结构揭示了其开放的构造. 体信号和体结合诱导构造变化,改变整合素亲和力.
科学领域:
- 结构生物学 结构生物学
- 免疫学 免疫学 免疫学
- 生物化学 生物化学
背景情况:
- 整体素,像α L beta 2一样,是关键的细胞表面受体,参与细胞粘附和免疫反应.
- 阿尔法Lβ2的I域对于与其连接体ICAM-1结合至关重要,该连接体是免疫球蛋白超级家族 (IgSF) 的成员.
- 了解这种相互作用的结构基础是解读免疫细胞贩运和激活的关键.
研究的目的:
- 确定与ICAM-1复合的整合素αLβ2I域的高分辨率结构.
- 阐明在整基因中依赖于连接体诱导的构造变化和亲和度调节的结构机制.
- 在原子层面描述第一个整合素-IgSF接口.
主要方法:
- 使用X射线结晶学来获得整合素α Lβ 2 I域的结构.
- 对高和中等亲和度变体进行了变异性研究.
- 二硫化物键的设计是为了探测构成状态.
主要成果:
- 该结构揭示了与ICAM-1结合的整合素α Lβ 2 I域的开放性联结构造.
- 观察到ICAM-1的I域中的Mg2+与Glu-34之间的直接协调,以及涉及Glu-241的盐桥.
- 带结合和质信号可以诱导从封闭状态到开放状态的结构变化,独立于带结合,调节亲和力.
结论:
- 该研究提供了第一个整合素-IgSF复合物的结构见,详细介绍了开放的联结体结合形状.
- 阿尔法L I域的形态灵活性允许全调节,使闭合状态,中间状态和开放状态之间的过渡成为可能.
- 设计的二硫化物键证明了通过稳定特定循环形状来调整整合素亲和力的机制.
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