大型瘤抗原的功能和结构比较分析揭示了不同importin α-依赖核定位信号的演变
Emily M Cross1,2, Nasim Akbari3, Hanieh Ghassabian3
1School of Dentistry and Medical Sciences, Charles Sturt University, Wagga Wagga, Australia.
Protein science : a publication of the Protein Society
|December 18, 2023
概括
在多瘤病毒大瘤抗原 (LTA) 中核定位信号 (NLS) 的演变显示出显著的多样性. 这些信号适应绑定importin-alpha,影响蛋白质运输和病毒功能.
科学领域:
- 细胞生物学 细胞生物学
- 病毒学 病毒学
- 分子进化分子进化
背景情况:
- 核细胞质运输对细胞功能至关重要,由进口蛋白质介导.
- 经典的核定位信号 (cNLSs) 通过importin-alpha和importin-beta1.1将蛋白质引导到核中.
- 对于cNLSs的进化和多样性,特别是在病毒蛋白中,仍然不完全理解.
研究的目的:
- 研究cNLSs在人类多瘤病毒 (HPyV) 大瘤抗原 (LTA) 的进化途径.
- 描述HPyV LTA cNLSs的结构和功能多样性以及它们与importin-alpha (IMPα) 异型体的相互作用.
- 阐明cNLS进化如何影响核积累和蛋白质功能.
主要方法:
- 对HPyV LTA序列的生物信息分析.
- 用于评估IMPα结合的生物化学测试.
- 核向和蛋白质定位的功能研究.
- 对cNLS-IMPα相互作用的结构分析.
主要成果:
- HPyV LTA cNLS在结构,IMPα异形结合和核准效率方面表现出显著的异质性.
- 经典的SV40 NLS在HPyV中没有得到保留;相反,不同的NLS已经演变.
- 默克尔细胞多重瘤病毒中的混合双元cNLS表现出可塑性,其中一部分作为非典型的NLS起作用.
- 进化机制包括NLS重复和点突变,优化IMPα结合部位相互作用.
结论:
- HPyV LTA cNLS 已经发展出各种核导入策略,适应不同的 IMPα 结合点.
- 这种进化可塑性使病毒能够调节核积累,并可能逃避宿主防御.
- 这项研究揭示了核定位信号的分子演变及其对病毒蛋白的功能影响的新见解.
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