Structural studies of the spliceosome: zooming into the heart of the machine.

Structural studies of the spliceosome: zooming into the heart of the machine.
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DOI:
10.1016/j.sbi.2013.12.002
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发表时间:
2014-04
影响因子:
6.8
通讯作者:
Nagai K
Nagai K
中科院分区:
生物学2区
文献类型:
--
作者:
Galej WP;Nguyen TH;Newman AJ;Nagai K

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Prp8和Brr2的结构已经确定。剪接体活性部位腔体的洞察。剪接体和II族内含子之间新的进化联系。已经发现了催化镁离子的配体。剪接体是一种大型的动态核糖核蛋白复合物,通过两步剪接反应催化信使RNA前体中内含子的去除。Prp8最近的晶体结构揭示了逆转录样结构域、连接体和核内切酶样结构域。内含子分支点与活性剪接体中Prp8的Linker结构域交联,并与5 ‘和3 ’剪接位点突变的抑制子一起,明确定位了活性位点空腔。与II族自剪接内含子的结构和机制相似性促使人们认为剪接体的核心是核酶,最近在U6 snRNA中发现了两种催化镁离子的配体。它们以与II族内含子RNA结构域V相同的方式定位催化二价金属离子,这表明剪接体和II族内含子使用相同的催化机制。
Structures of Prp8 and Brr2 have been determined. Insights into the active site cavity of the spliceosome. New evolutionary links between spliceosomes and group II introns. Ligands of the catalytic magnesium ions have been found. Spliceosomes are large, dynamic ribonucleoprotein complexes that catalyse the removal of introns from messenger RNA precursors via a two-step splicing reaction. The recent crystal structure of Prp8 has revealed Reverse Transcriptase-like, Linker and Endonuclease-like domains. The intron branch-point cross-link with the Linker domain of Prp8 in active spliceosomes and together with suppressors of 5′ and 3′ splice site mutations this unambiguously locates the active site cavity. Structural and mechanistic similarities with group II self-splicing introns have encouraged the notion that the spliceosome is at heart a ribozyme, and recently the ligands for two catalytic magnesium ions were identified within U6 snRNA. They position catalytic divalent metal ions in the same way as Domain V of group II intron RNA, suggesting that the spliceosome and group II intron use the same catalytic mechanisms.
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