结构性转型调整了Grp94的陪伴活动
Yaa S Amankwah1,2, Yasmeen Fleifil1, Erin Unruh1,3
1Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056.
概括
热冲击蛋白90 (Hsp90) 和其ER同类Grp94与BiP陪伴系统合作,用于客户端蛋白质折叠. DnaJB11辅助子促进了这种相互作用,调节了Grp94的作用.
科学领域:
- 分子生物学分子生物学
- 蛋白质折叠 蛋白质的折叠
- 细胞应激反应的应激反应
背景情况:
- 热冲击蛋白 (Hsp90s) 是依赖ATP的伴侣,对于蛋白质重塑至关重要.
- Grp94是Hsp90的内质网膜 (ER) 同类物,对于折叠分泌和膜蛋白至关重要.
- Grp94和ER Hsp70陪伴BiP之间的准确协作机制尚不清楚.
研究的目的:
- 阐明Grp94的陪伴机制,重点关注其与BiP的合作.
- 调查 Grp94 的 pre-N 域在陪伴者活动和客户互动中的作用.
- 描述Grp94,BiP和辅导员之间的结构和功能相互作用.
主要方法:
- 集成的体内和体外功能测定.
- 结构研究以确定Grp94的结构.
- 对Grp94-客户端和Grp94-BiP相互作用的分析.
主要成果:
- Grp94直接与BiP护送系统合作,用于客户端折叠.
- Grp94的pre-N域抑制了它的ATP水解和活性构造.
- 同伴 DnaJB11 促进 Grp94-BiP 相互作用,激活 Grp94 的 ATP 酶活性.
- ATP和BiP结合合作诱导Grp94的活性闭合形状.
- 核酸结合降低了Grp94的客户亲和力,促进了生产性的折叠.
结论:
- Grp94的陪伴活动由其前N域调节,并由BiP和DnaJB11调节.
- 受到核酸结合和协伴蛋白的影响的Grp94-BiP协作对于客户端蛋白质折叠至关重要.
- 核酸依赖的客户端亲和度调节可能代表ER陪伴者中保留的机制.
关键词:
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