狗间流素-31直接与OSMRβ结合,结合亲和力比IL-31RA高
Yuxin Zheng1,2,3, Jing Zhang2,3, Tianling Guo2,3
1College of Biological Engineering, Tianjin University of Science and Technology, Tianjin, 300457 China.
3 Biotech
|August 17, 2023
概括
狗类介质素-31 (IL-31) 与其受体结合,即狗类IL-31受体α (cIL-31RA) 和狗类哥斯塔丁M受体子单元β (cOSMRβ). 狗IL-31对cOSMRβ的亲和力明显高于对cIL-31RA的亲和力.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 介素-31 (IL-31) 是一种促炎性细胞因子,与皮肤炎症和瘤进展有关.
- IL-31通过结合IL-31受体α (IL-31RA) 和色素M受体子单元β (OSMRβ) 来启动信号传递.
- 虽然人类和猫类IL-31的结合模式已被部分理解,但犬类IL-31受体的相互作用仍然不清楚.
研究的目的:
- 描述复合犬类IL-31 (rcIL-31) 对其同类受体的结合特性.
- 阐明rcIL-31对犬类IL-31RA和犬类OSMRβ (cOSMRβ) 的结合亲和性和特异性.
- 为了在cOSMRβ中确定参与rcIL-31结合的关键域.
主要方法:
- 再组合犬 IL-31 (rcIL-31) 的净化和二次结构分析.
- 在体外评估rcIL-31在DH-82细胞中诱导STAT3和STAT5酸化的能力.
- 流细胞计测试测量rcIL-31与细胞表面表达的cIL-31RA和cOSMRβ.的结合功效.
- 使用表面等离子共振 (SPR) 对rcIL-31与可溶性cOSMRβ的亲和度测量.
主要成果:
- rcIL-31的二次结构主要是α-螺旋.
- rcIL-31在DH-82细胞中诱导了STAT3和STAT5酸化,表明了生物活性.
- rcIL-31独立地与cIL-31RA和cOSMRβ结合,在细胞表面表达.
- 与cIL-31RA相比,rcIL-31对cOSMRβ的结合亲和力高出十倍以上.
- 确定cOSMRβ的D1-D4域,特别是D4,对于rcIL-31结合至关重要.
- 确定了rcIL-31与可溶性cOSMRβ的高结合亲和力,其KD值为3.59 × 10−8 M.
结论:
- 这项研究成功地描述了犬类IL-31与其受体,cIL-31RA和cOSMRβ.的结合.
- 狗类IL-31表现出强烈的偏好与cOSMRβ结合,而不是cIL-31RA.
- 这些发现为犬类IL-31受体相互作用提供了关键的见解,并对开发针对犬类IL-31介导疾病的向治疗有意义.
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