对库林-RING酶的NEDD8激活的结构洞察:对结合的结构控制
David M Duda1, Laura A Borg, Daniel C Scott
1Howard Hughes Medical Institute, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Cell
|September 23, 2008
概括
库林-RING酶 (CRLs) 的活性由NEDD8修改控制. 这种结构变化不利于不活跃的形式,促进多基化和增强CRL功能.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 库林-RING连接酶 (CRL) 是一种主要的ubiquitin E3酶类.
- 对CRL的NEDD8修改激活了它们的泛化活性,并抑制了CAND1结合.
研究的目的:
- 在NEDD8修改后调查CRL的结构和构造变化.
- 了解这些变化如何影响CRL活性和抑制剂结合.
主要方法:
- 在NEDD8修改后的Cul5 (((ctd) -Rbx1.1.的X射线晶体学.
- 小角度X射线散射 (SAXS) 的NEDD8-修改的Cul1(ctd) -Rbx1.
- 生物化学测试以评估无处不在的活性.
主要成果:
- 在CRL中,NEDD8修改引发了显著的结构重组.
- 库林WHB和Rbx1 RING子域重定位,消除了CAND1结合点.
- 结构形性对于NEDD8ylation和随后的无处不在都至关重要.
结论:
- NEDD8结合将CRL从不活跃的,封闭的形状转移到动态的,开放的形式.
- 这种由NEDD8进行的构造控制促进了多基化,并增强了CRL的活性.
- 这些发现揭示了CRL功能中构造性调节的机制.
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