虹膜素通过其整合素受体在两步过程中作用,涉及细胞外Hsp90αα
Mu A1, Thomas E Wales2, Haixia Zhou3
1Department of Cancer Biology, Dana-Farber Cancer Institute, 360 Longwood Avenue, Boston, MA 02215, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Molecular cell
|June 2, 2023
概括
运动通过虹膜激素增强认知和神经保护. 这项研究揭示了细胞外热冲击蛋白90α (eHsp90α) 促进了虹膜素与整合素αVβ5的结合,揭示了一种新的信号通路.
科学领域:
- 分子生物学分子生物学
- 运动生理学 运动生理学
- 神经科学是一个神经科学.
背景情况:
- 运动带来许多健康益处,包括改善认知和神经保护.
- 肌肉分泌的激素虹膜,通过与整合素相互作用来调解其中一些益处.
- 素通过整体素传递信号的确切机制尚不清楚.
研究的目的:
- 阐明通过整合素受体传递素信号的分子机制.
- 为了确定参与虹膜介导信号传递的特定整合素子单元.
- 描述素-整合素相互作用的结构基础.
主要方法:
- 质谱学和冷电子显微镜 (cryo-EM) 用于分析蛋白质复合体.
- /交换质谱 (HDX-MS) 提供了对蛋白质动态和结合接口的洞察.
- 用结构建模和实验验证来确定素/整合素复合结构.
主要成果:
- 细胞外热冲击蛋白90α (eHsp90α) 在运动期间由肌肉分泌,并激活整合蛋白αVβ5.5.
- 一个Hsp90α/αVβ5的三元复合体促进了虹膜素与αVβ5.5整合素的高亲和结合.
- 虹膜素与αVβ5上的另一个接口结合,与已知的联结位点不同.
- 一个高分辨率 (2.98 Å RMSD) 的虹素/αVβ5复合物的对接模型被生成和验证.
结论:
- 运动诱导的eHsp90α充当关键的共受体,使虹素能够通过整合素αVβ5.5传递信号.
- 这项研究揭示了小聚类激素通过整基因传递信号的非正规机制.
- 这些发现为素对认知和神经保护的有益作用提供了机制基础.
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