进化和功能分析揭示了RHIM在调整脊椎动物RIPK3活动中的作用
Elizabeth J Fay1, Kolya Isterabadi1, Charles M Rezanka1
1Department of Molecular Biology, School of Biological Sciences, University of California, San Diego, La Jolla, CA, 92093.
bioRxiv : the preprint server for biology
|August 16, 2024
概括
受体相互作用蛋白激酶 (RIPK) RIPK1和RIPK3是天生的免疫的关键. 演变显示了RIPK3的存在.
科学领域:
- 免疫学 免疫学 免疫学
- 进化生物学 进化生物学
- 分子生物学分子生物学
背景情况:
- 受体相互作用蛋白激酶 (RIPK) RIPK1和RIPK3是先天免疫信号通路的关键组成部分.
- 脊椎动物谱系中RIPK1/3相关蛋白的变异表明它们的功能具有进化可塑性.
- 了解这些进化动态是解读保守与不稳定免疫机制的关键.
研究的目的:
- 在脊椎动物中进行RIPK1-5和相关蛋白质的比较进化分析.
- 为了确定RIPK家族内的快速,特定于血统的进化和蛋白质损失的实例.
- 调查RIPK3在先天免疫中的作用的功能性保护和进化调整.
主要方法:
- 在各种脊椎动物物种中对RIPK1-5和相关蛋白质进行比较的进化分析.
- 在人类细胞中进行功能性测试,以评估各种脊椎动物RIPK3蛋白的NF-κB和细胞死亡激活能力.
- 详细分析RIP同型相互作用动机 (RHIM) 在RIPK3和其他含有RHIM的蛋白质中的保存和序列多样性.
主要成果:
- 在RIPK3和RIPK1中确定了特定系的快速进化,以及RIPK3相关蛋白的反复损失.
- 证明各种脊椎动物RIPK3蛋白可以激活NF-κB并诱导人类细胞中的细胞死亡.
- 揭示了RIPK3中RIP同型相互作用动机 (RHIM) 的惊人保存,其序列多样性能够调节NF-κB激活,同时保留细胞死亡功能.
结论:
- NF-κB激活代表了RIPK3.3的一个核心,进化保守的功能.
- RIP同型相互作用基因 (RHIM) 作为一个关键的结构元素,可以在不同物种中微调RIPK3的免疫功能.
- RHIM的进化多样化使RIPK3能够将其信号输出适应特定物种的要求,平衡保存和不稳定的功能.
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