分子黏附中的逆锁键研究进展
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作者单位:

1.1)复旦大学化学系,上海 200433;2.2)复旦大学大数据学院,上海 200433

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Tel: 13332921593, E-mail: caox16@fudan.edu.cnTel: 86-13332921593, E-mail: caox16@fudan.edu.cn

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基金项目:

复旦大学启明星科创计划


Research Progress of Catch Bonds in Molecular Adhesion
Author:
Affiliation:

1.1)Chemistry Department, Fudan University, Shanghai 200433, China;2.2)School of Data Science, Fudan University, Shanghai 200433, China

Fund Project:

This work was supported by a grant from Fudan University Science and Technology Development Funds(2016-2017-016).

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    摘要:

    逆锁键是受体和配体蛋白质相互作用过程中的一种“反常”现象,属于受体-配体动态键的一种,在pN量级外力的影响下,其键寿命在特定范围内会随着所施加外力的增加而增加. 逆锁键主要参与细胞黏附、细胞活化等过程,并与滑移键组成分子开关来调节各项与分子黏附相关的生命活动. 其中,致病性大肠杆菌引发尿路感染、T细胞受体抗原识别、微丝解聚、Notch信号通路激活等重要生命活动已被证实与逆锁键密切相关. 近期已有发现证实TCR-pMHC复合物中的逆锁键与癌症的引发也存在密切联系,这一发现提供了改进TCR-T(T细胞受体基因工程改造的T细胞)免疫疗法的新方向. 本文概述了逆锁键在几类重要生命活动中的最新研究进展,并讨论了其潜在的医学研究前景.

    Abstract:

    Catch bond is a type of dynamic bond that exists in receptor protein and ligand interactions. The bond lifetime of catch bond is positively correlated with the pN-level external force that applied onto it within a certain range. Catch bond is mainly involved in cell adhesion and cell activation processes and it forms molecular switch with slip bond to regulate cell adhesion related cell activities. Catch bond has proven link with the urinary tract infection process that initiated by the pathogenic E. coli, T cell receptor-antigen recognition, microfilament depolymerization and Notch signaling pathway activation. This review summarized the progresses and new findings of catch bond research in cell adhesion, T cell activation, actin interaction. For cell adhesion of prokaryotes and eukaryote, catch bonds exist in a wide range of related proteins, including FimH, selectin, integrin. For T cell activation, recent research revealed that the catch bond in TCR-pMHC interaction is closely related to cancer cell development processes and this finding provides a new direction in improving T cell receptor-gene engineered T cells (TCR-T) immunotherapy. For actin interaction, the actin catch bond has been proven involving in RhoA-formin switch force-induced actin cytoskeleton alignment process. To further illustrate the prospect of catch bonds in medical research, we also discussed the potential of catch bonds in the development of anti-bacterial or anti-adhesion drugs and improvement for the TCR-T immunotherapy.

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引用本文

曹旭,常晟源.分子黏附中的逆锁键研究进展[J].生物化学与生物物理进展,2021,48(6):637-645

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  • 收稿日期:2020-08-02
  • 最后修改日期:2020-10-03
  • 接受日期:2020-12-02
  • 在线发布日期: 2021-06-24
  • 出版日期: 2021-06-20
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