在脊椎动物进化过程中,NF-κB家族成员Rel的逐步新功能化
Allison E Daly1,2, Abraham B Chang1,2, Prabhat K Purbey1,2,3
1Department of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA, USA.
Nature immunology
|April 30, 2025
概括
这是一种NF-κB Rel蛋白.
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:
- 适应性免疫和NF-κB (激活B细胞的核因子卡帕-光链增强剂) 家庭成员起源于早期的脊椎动物.
- NF-κB Rel蛋白在激活Il12b中发挥作用,Il12b是T细胞发育的关键调节者.
研究的目的:
- 研究脊椎动物进化过程中NF-κB Rel二极体及其向基因,特别是Il12b的进化过渡.
- 了解Rel二极体增强的DNA结合亲和力及其在免疫调节中的作用的结构基础.
主要方法:
- 全基因组染色体免疫沉,然后进行测序 (ChIP-seq) 以映射NF-κB结合部位.
- 进行X射线晶体学以确定Rel二极体DNA结合亲和力的结构基础.
- 在脊椎动物物种之间对Il12b调节的比较分析.
主要成果:
- 通过NF-κBRel二极体激活Il12b,显示对Rel的依赖性比天生的免疫基因更大.
- 确定了一种特定的残留物,它与Rel二极体具有较高的DNA结合亲和力.
- 这种增强的亲和力和特定的Il12b促进体结合在很大程度上仅限于哺乳动物,表明了晚期的进化过渡.
结论:
- 在NF-κB Rel及其Il12b促进体的主要结构变化发生在脊椎动物进化的晚期.
- 这些转变重新连接了免疫调节途径,导致哺乳动物免疫系统的复杂性.
- 提升Rel二极体DNA结合亲和力的进化对于专门的免疫功能至关重要.
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