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开发具有选择性降低肝素硫酸盐亲和度的FGF2突变,以探索它们对FGFR1信号传递的影响

Yuga Okada¹, Akihiro Eguchi², Daisuke Kuroda¹

¹The University of Tokyo: Tokyo Daigaku, Department of Chemistry and Biotechnology, JAPAN.

Chembiochem : a European journal of chemical biology

|July 8, 2025

概括

纤维细胞生长因子2 (FGF2) 与肝素硫酸盐 (HS) 的相互作用可能在FGF2/FGFR1信号传递中起到有限的作用. 这项研究设计了FGF2突变体,以探测细胞信号传递中的FGF2/HS相互作用.

科学领域:

生物化学生物化学
分子生物学分子生物学
细胞信号传递细胞信号传递

背景情况:

纤维细胞生长因子2 (FGF2) 和其受体 (FGFRs) 是生物过程的关键调节者.
建议肝素硫酸盐 (HS) 作为调节FGF/FGFR信号的共同受体,但其确切的作用尚不清楚.

研究的目的:

研究FGF2/HS相互作用在FGF2/FGFR1信号传递中的特定作用.
阐明 HS 影响 FGF/FGFR 信号通路的机制.

主要方法:

使用in silico分析合理设计具有显著降低HS结合亲和度的FGF2突变.
在HS亲和力,FGFR1结合亲和力和热稳定性方面对FGF2突变的表征.
细胞测试以评估改变的FGF2/HS相互作用对FGF2/FGFR1信号传递的影响.

主要成果:

FGF2突变体在HS亲和力下降100倍以上,同时保持FGFR1结合和热稳定性.
细胞测试表明,FGF2/HS相互作用对FGF2/FGFR1信号传递的贡献可能比以前报告的要少.
开发的突变特异性破坏了FGF2-HS相互作用,为进一步调查提供了一个工具.

结论:

FGF2/HS相互作用对FGF2/FGFR1信号的直接贡献似乎有限.
这项研究提供了新的FGF2突变,这将有助于剖析HS在生长因子信号传导中的复杂作用.
需要进一步的研究,以充分理解FGF,FGFR和HS在生物系统中的相互作用.

关键词:

增长因子 * 受体 * 蛋白质设计 * 信号传导 * 肝素硫酸盐

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