纤维细胞生长因子受体 (ectodomain) 的晶体结构与连接体和肝素结合
L Pellegrini1, D F Burke, F von Delft
1Department of Biochemistry, University of Cambridge, UK. luca@cryst.bioc.cam.ac.uk
Nature
|November 9, 2000
概括
这项研究揭示了纤维细胞生长因子 (FGF) 信号复合体的晶体结构. 该结构阐明了硫酸在调解FGF和细胞信号传递的受体相互作用方面的重要作用.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 纤维细胞生长因子 (FGF) 是各种生理和病理过程中的关键蛋白质.
- FGF信号依赖于FGF的三元复合体,其受体氨酸激酶 (FGFR) 和肝素硫酸盐蛋白质糖.
- 这种信号复合体的精确分子结构在很大程度上是未知的.
研究的目的:
- 为了阐明FGF信号复合体的分子结构.
- 为了确定FGF1和肝素结合的FGFR2ectodomain的晶体结构.
- 为甲酸在FGF信号传导中的作用提供结构基础.
主要方法:
- 采用X射线晶体学来确定三元复合物的结构.
- 该复合体由FGFR2ectodomain,FGF1和一个氨酸脱糖化物组成.
- 结构分析侧重于组装的信号复合体内的相互作用.
主要成果:
- 晶体结构揭示了由FGF1和氨酸结合诱导的FGFR2ectodomain的二元形式.
- 一个中央的氨酸分子连接了两个FGF1连接体,这反过来又连接了两个受体链.
- 肝素结合是不对称的,与FGF1分子相互作用,但只与一种受体链相互作用.
结论:
- 确定的结构提供了FGF-FGFR-heparan硫酸盐三元复合物的第一个详细的分子视图.
- 这种结构突出显示了甲酸作为FGF信号传递所必需的分子支架的关键作用.
- 这些发现为了解FGF介导的生物活动提供了结构性基础.
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