对子SAMD9的结构和功能研究揭示了一个独特的tRNase模块,它是抗病毒活动的基础
bioRxiv : the preprint server for biology
|April 28, 2025
概括
无菌阿尔法基因域含有9 (SAMD9) 和SAMD9类 (SAMD9L) 蛋白质对于抗病毒防御至关重要. 子SAMD9 (rSAMD9) 尽管具有独特的结构变异,但仍然保留了tRNA分裂和抗病毒功能,证明了进化灵活性.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 结构生物学 结构生物学
背景情况:
- 无菌阿尔法基因域含有9 (SAMD9) 和SAMD9-like (SAMD9L) 是哺乳动物蛋白质,具有既定的抗病毒和抗增殖功能.
- 这些蛋白质通过分裂氨酸tRNA (tRNAPhe) 来调节蛋白质合成,其关键活性位于N-终端tRNase域.
- 在tRNase域中保存的基本残留物对人类SAMD9 (hSAMD9) 活动至关重要,但在这些部位之一的Lagomorph SAMD9 orthologs 具有独特的酸性残留物.
研究的目的:
- 调查 SAMD9 (rSAMD9) 的抗病毒和tRNA分裂活动,考虑到与hSAMD9.9相比,其独特的序列变异.
- 描述rSAMD9.9的tRNase模块中的结构和功能差异.
- 了解SAMD9/SAMD9L功能的进化性保护和灵活性.
主要方法:
- 功能性测试用于评估表达rSAMD9.9的细胞中的疫苗病毒限制和tRNAPhe水平.
- 结构分析,包括确定rSAMD9tRNase模块 (氨基酸158-389) 的晶体结构.
- 序列比较和突变分析以确定rSAMD9活动的关键残留物.
主要成果:
- SAMD9 (rSAMD9) 有效地限制了疫苗病毒的复制,并降低了tRNAPhe水平,类似于hSAMD9.
- rSAMD9的功能性tRNase模块超越了保存域,包括SIR2区域,包含了额外的重要基本残留物,其中一个是rSAMD9.9独有的.
- rSAMD9158-389的晶体结构与hSAMD9156-385相似,在环形状上有显著的差异.
结论:
- 拉哥形SAMD9正基因保持了重要的tRNA向和抗病毒功能,尽管关键残留物中发生了电荷逆转突变.
- rSAMD9使用扩展的tRNase模块,包括SIR2区域和独特的基本残留物,以实现其生物活性.
- 这些发现突显了SAMD9/SAMD9LtRNase模块的进化适应性,同时保留了核心功能.
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