不硫化物桥依赖的二分化触发了FGF2膜转移到细胞外空间的过程
Fabio Lolicato1,2, Julia P Steringer1, Roberto Saleppico1
1Heidelberg University Biochemistry Center, Heidelberg, Germany.
eLife
|January 22, 2024
概括
纤维细胞生长因子2 (FGF2) 的分泌涉及膜孔形成. 通过C95形成的二硫化物桥接FGF2二聚体是寡合化,孔隙形成和FGF2跨细胞膜转移的关键.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 分子生物学分子生物学
背景情况:
- 纤维细胞生长因子2 (FGF2) 通过非传统的蛋白质分泌而分泌.
- 通过血转移FGF2需要PI(4,5) P2和细胞表面GPC1.1.
- 在分泌过程中FGF2寡合化的分子机制尚未完全理解.
研究的目的:
- 阐明FGF2寡合化和膜转位的分子机制.
- 为了研究半氨酸残留物 (C95和C77) 在FGF2分泌中的作用.
- 了解FGF2与Na,K-ATPase的相互作用.
主要方法:
- 位点定向的突变发生 (C95A替代).
- 交叉连接质谱仪. 交叉连接质谱仪.
- 原子分子动力学模拟和机器学习分析.
- 冷电子断层扫描.
主要成果:
- 在膜表面的C95-C95二硫化物桥介导二聚化中,FGF2的寡聚化开始了.
- C95A的替代破坏了FGF2的寡合化,孔隙形成和膜转位,导致严重的分泌缺陷.
- C77参与与Na,K-ATPase结合,但不参与FGF2的寡合化.
- 与二硫化物桥接的FGF2二极体激烈地与PI{4,5) P2结合,从而启动孔隙形成.
结论:
- 通过C95介导的二硫化物桥接FGF2二极体是FGF2寡合化和分泌的重要组成部分.
- FGF2分泌与信号复合体的形成密切相关,C95桥梁二次体可能触发自身隐性/隐性信号.
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