一种鱼类I型的结构和功能表征子组 d IFN揭示了它与受体的结合
Yanyun Guan1, Jingjie Chen1, Hongxin Guan2
1State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou, China.
Journal of immunology (Baltimore, Md. : 1950)
|February 12, 2024
概括
鱼类型I干扰素 (IFN) 使用CRFB1和CRFB5受体来激活抗病毒反应. 结构分析揭示了鱼类和哺乳动物类型I IFN及其受体之间的独特结合机制.
科学领域:
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
- 鱼类生物学 鱼类生物学
背景情况:
- I型干扰素 (IFN) 和它们的受体在远鱼中表现出显著的多样性.
- 鱼类I型IFN及其同类受体之间的精确结合相互作用在很大程度上仍然没有特征.
研究的目的:
- 为了阐明大黄 (Larimichthys crocea) 中I型子组d IFN (IFNd) 的受体使用和结合机制.
- 研究IFNd受体相互作用的结构基础,并将其与哺乳动物对应物进行比较.
主要方法:
- 结晶学被用来确定L.crocea IFNd (LcIFNd) 的结构.
- 使用结构建模来预测LcIFNd与L. crocea CRFB1 (LcCRFB1) 和LcCRFB5 (LcCRFB5) 的复合体.
- 进行了结合亲和度测试,以评估LcIFNd与LcCRFB1和LcCRFB5.5的相互作用.
主要成果:
- LcIFNd利用受体对CRFB1和CRFB5来激活JAK-STAT信号通路.
- 与LcCRFB1.1.相比,LcIFNd对LcCRFB5的结合亲和力更高.
- 结构分析揭示了teleost和哺乳动物I型IFN之间的明显受体结合接口,其中涉及的关键残留物大致不同.
结论:
- 在远鱼中,CRFB1和CRFB5形成了LcIFNd的功能性受体综合体.
- 这项研究揭示了远鱼中IFNd的独特的连接体/受体结合机制.
- 研究结果提供了对脊椎动物I型IFN的演变和功能分歧的关键见解.
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