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通过Cdc48 ATPase复合体处理基质的分子机制
Nicholas O Bodnar1, Tom A Rapoport1
1Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Cell
|May 6, 2017
概括
具有Ufd1/Npl4 (UN) 辅因子的Cdc48 ATPase复合体解并提取多基化蛋白质. ATP水解驱动基质的转移和释放,需要二基因酶的合作.
科学领域:
- 蛋白质生物化学
- 分子细胞生物学
- 酵素学
背景情况:
- Cdc48 ATPase 和 Ufd1/Npl4 (UN) 对于从细胞结构中提取多基因蛋白质至关重要.
- Cdc48复合体对基质的精确处理机制在很大程度上仍未确定.
研究的目的:
- 阐明Cdc48-UN复合物处理多基化蛋白质的逐步机制.
- 了解D1和D2 ATPase环在基质展开和释放中的不同作用.
主要方法:
- 使用纯化的Cdc48,Ufd1/Npl4 (UN) 辅因子和多基化蛋白质基底的生物化学测试.
- 在Cdc48双环结构中对依赖ATP水解的基质转位和展开的分析.
主要成果:
- D2环的ATP水解驱动基质多转移通过中央孔隙,诱导展开.
- D1环的ATP水解对于随后从复合物中释放基质至关重要.
- 基质释放需要与二基因酶合作,以切割多基因链以进行转位.
结论:
- 提出了一种新的Cdc48介导蛋白质提取模型,涉及不同的环中的顺序ATP水解事件.
- 这些发现突显了Cdc48,其辅助因子和二维基因酶在蛋白质加工和降解途径中的协调作用.
- 这种机制为Cdc48及其哺乳动物同类物p97/VCP的功能提供了洞察力.
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