类型I和类型II的完整细胞外组合的结构 哥斯塔丁M受体复合体
Yi Zhou1, Panayiotis E Stevis2, Jing Cao2
1Regeneron Pharmaceuticals, Inc., Tarrytown, NY, 10591, USA. yi.zhou@regeneron.com.
Nature communications
|November 12, 2024
概括
使用冷EM揭示了可斯塔丁M (OSM) 受体复杂结构. 这些发现揭示了OSM如何发出信号,并为开发针对炎症性疾病和癌症的新疗法提供了见解.
科学领域:
- 结构生物学是结构生物学.
- 分子和细胞生物学分子和细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 哥斯塔丁M (OSM) 是一种IL-6家族的细胞因子.
- OSM通过两个受体复合体发出信号:I型 (gp130/LIFR) 和II型 (gp130/OSMR).
- OSM与炎症性疾病和癌症有关,使其成为治疗点.
研究的目的:
- 描述人类I型和小鼠II型OSM受体复合体的细胞外组件.
- 阐明OSM受体复合体形成和信号的结构基础.
- 为OSM信号的治疗调制提供见解.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定结构.
- 进行了变异性研究,以确定复杂形成和信号的关键残留物.
主要成果:
- 确定了I型和II型OSM受体复合物的结构.
- 由于受体曲,受体柔膜域非常接近.
- OSM的N端延伸对于gp130的结合和信号传递至关重要;糖化和前域裂变不会影响活性.
- 确定了涉及复杂组装和信号的关键OSM和OSMR残留物.
结论:
- 该研究揭示了OSM I型和II型受体复合组合的结构基础.
- 了解这些结构为开发有针对性的治疗提供了基础.
- 获得的见解可以指导OSM信号通路的调制,以获得治疗效益.
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