选择压力调节单细胞化学吸引蛋白家族的进化-结构-功能范式
Nupur Nagar1, Khushboo Gulati1, Krishna Mohan Poluri2,3
1Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, 247667, India.
Journal of molecular evolution
|February 5, 2025
概括
单细胞化学吸引蛋白 (MCP) 通过受体/GAG结合部位的替代进化了多种功能. 选择压力对它们的相互作用和特性进行了微调,同时保留了核心的化学因子结构.
科学领域:
- 进化生物学是进化的生物学.
- 免疫学 免疫学 免疫学
- 结构生物学是结构生物学.
背景情况:
- 单细胞化学吸引蛋白 (MCP) 是单细胞在炎症中贩运的关键调节者.
- 许多细胞共聚因子 (CCL2,CCL7,CCL8,CCL13/12) 的表达,功能和与受体和葡萄糖氨基酸甘 (GAG) 的结合是多样化的.
研究的目的:
- 为了研究哺乳动物MCP化学因子的进化-结构-功能范式.
- 了解进化压力如何塑造MCP多样性和相互作用.
主要方法:
- 人类遗传学分析
- 功能差异评估的功能差异评估
- 选择压力分析选择压力分析
- 共同进化的研究.
- 结构生物信息学 结构生物信息学
- 分子动力学模拟的模拟.
主要成果:
- 受体/GAG相互作用残留物的替代驱动MCP多样化和功能多样性.
- 在结合部位的积极选择促进了乱交的受体/GAG相互作用.
- 净化选择和共同进化维持了化基因结构和祖先的功能.
- 在特定区域 (N-终端,40S循环) 上的选择改变了表面特性,而没有改变整体结构.
结论:
- 进化压力,特别是在受体/GAG结合部位,已经塑造了MCP化学因子的功能多样性.
- 选择力量的平衡保持了结构完整性,同时允许功能适应.
- 了解这些进化机制,可以深入了解化学介导的炎症反应.
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