在进化过程中,C反应性蛋白的保存功能是防止粉样纤维的形成
Alok Agrawal1, Asmita Pathak1, Donald N Ngwa1
1Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States.
C-反应蛋白 (CRP) 古代与粉样β (Aβ) 结合,以防止其有害的纤维化. 这项研究表明,马的CRP在没有结构变化的情况下与Aβ结合,揭示了在进化过程中保留的对粉样的保护功能.
科学领域:
- 免疫学 免疫学 免疫学
- 进化生物学 进化生物学
- 生物化学 生物化学
背景情况:
- C-反应蛋白 (CRP) 是一种关键的急性阶段蛋白质,以结合胆 (PCh) 和激活补充而闻名.
- 人类CRP与β-粉样蛋白 (Aβ) 结合,并抑制其纤维化,但该功能的进化保存是未知的.
- CRP的PCh结合在物种之间得到保护,这表明了除了补充激活之外的潜在古老作用.
研究的目的:
- 为了调查美国马 (Limulus polyphemus) 的CRP是否表现出抗粉原性质.
- 确定是否需要进行结构性改变,以使Limulus CRP (Li-CRP) 能够结合Aβ.
- 探索CRP的Aβ结合能力的进化起源.
主要方法:
- 使用PCh亲和和甲胺亲和染色法净化两个Li-CRP物种 (Li-CRP-I和Li-CRP-II).
- 在生理pH下对不动态和流体相Aβ的Li-CRP结合的评估.
- 使用离子交换色谱分析Li-CRP子单位组成.
主要成果:
- 两种Li-CRP-I和Li-CRP-II都与固定和流体相Aβ结合.
- 与人类CRP不同,Li-CRP不需要结构变化来结合Aβ.
- 在Limulus hemolymph.中发现了多种具有不同亚单元组成的Li-CRP物种.
结论:
- CRP结合Aβ的能力是一个古老的,进化保存的功能.
- 在无脊椎动物中,Li-CRP可能会保护它们免受有毒的amyloidogenic蛋白质的影响.
- 在人体中,CRP的Aβ结合功能可以保护人们免受炎症性疾病的影响,这些炎症性疾病涉及具有Aβ样结构的错误沉积蛋白质.
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