HSP40蛋白使用特定类别的调节来驱动HSP70的功能多样性
Ofrah Faust1, Meital Abayev-Avraham1, Anne S Wentink2
1Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
Nature
|November 12, 2020
概括
热冲击蛋白70 (HSP70) 的活性由J域蛋白 (JDP) 调节. 像DNAJB1一样,B类JDP使用独特的自抑制机制来执行HSP70的护送功能,这对于粉样蛋白分离至关重要.
科学领域:
- 分子生物学
- 蛋白质折叠
- 细胞应激反应
背景情况:
- 热冲击蛋白70 (HSP70) 是对蛋白质平衡至关重要的ATP依赖分子伴侣.
- 通过选择基质并刺激ATP水解,J域蛋白调节HSP70活动.
- 该JDP家族庞大且多样化,有40多名人类成员表现出多样化的基质选择性和客户端绑定领域.
研究的目的:
- 研究JDP与HSP70的相互作用的根本差异.
- 阐明管理联合开发计划,特别是B类联合开发计划的监管机制.
- 了解JDP调节在HSP70介导的细胞功能中的作用,例如粉样分离.
主要方法:
- 用核磁共振 (NMR) 光谱来研究JDP- HSP70的相互作用.
- 分析的重点是B类JDP中存在的自身抑制机制.
主要成果:
- 由DNAJB1所示的B类JDP具有在其他JDP类中缺少的自身抑制机制.
- 在DNAJB1中,J域内的HSP70结合位本质上被一个富含甘氨酸和氨酸的区域阻断.
- 这种抑制通过第二个DNAJB1位点与HSP70C终端尾部的相互作用释放,控制基质向.
结论:
- 在B类JDP中,自抑制机制对于HSP70介导的粉样纤维分解至关重要.
- 这一监管层规定了JDP的功能特点和HSP70的相互作用,解释了为什么B类JDP对于这个功能是不可替代的.
- 这种调节机制可能是HSP70广泛细胞作用的关键.
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