Structure of the spliceosomal U4 snRNP core domain and its implication for snRNP biogenesis.
Structure of the spliceosomal U4 snRNP core domain and its implication for snRNP biogenesis.
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DOI：
10.1038/nature09956
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发表时间：
2011-05-26
期刊：
影响因子：
64.8
通讯作者：
Li, Jade
中科院分区：
文献类型：
--
作者：
Leung, Adelaine K. W.;Nagai, Kiyoshi;Li, Jade
剪接体是一种动态的大分子机器，它在mrna前底物上组装并催化非编码中间序列（内含子）的切除。剪接体的5个主要组成部分（U1、U2、U4和U5 snRNPs）中有4个共同含有7个Sm蛋白（SmB/B’、SmD1、SmD2、SmD3、SmE、SmF和SmG）。在U1， U2， U4和U5 snRNA输出到细胞质后，由运动神经元存活（SMN）复合体陪同的7个Sm蛋白在每个snRNA中围绕称为Sm位点的单链富u序列组装，形成各自snRNP颗粒的核心结构域。核心结构域的形成是重新导入细胞核的先决条件，在细胞核中，这些snRNPs通过添加其颗粒特异性蛋白质而成熟。在这里，我们以3.6 Å分辨率展示了U4 snRNP核心结构域的晶体结构，详细介绍了Sm位点七聚体（AUUUUUG）如何在Sm蛋白七聚体环的中心孔内结合，并与SmE-SmG-SmD3-SmB-SmD1-SmD2-SmF进行一对一的相互作用。Sm位点序列的不规则主干构象与异质蛋白环的不对称结构相结合，使得每个碱基以独特的方式与Sm折叠的L3和L5环中等效位置的四个关键残基相互作用。该结构与U1 snRNP在5.5 Å分辨率下的比较揭示了Sm折叠外snrna依赖的结构变化，这可能促进颗粒特异性蛋白的结合，这对剪接体snRNP的生物发生至关重要。
The spliceosome is a dynamic macromolecular machine that assembles on pre-mRNA substrates and catalyses the excision of non-coding intervening sequences (introns). Four of the five major components of the spliceosome, U1, U2, U4 and U5 snRNPs, contain seven Sm proteins (SmB/B’, SmD1, SmD2, SmD3, SmE, SmF and SmG) in common. Following export of the U1, U2, U4 and U5 snRNAs to the cytoplasm, the seven Sm proteins chaperoned by the survival of motor neurons (SMN) complex assemble around a single-stranded, U-rich sequence called the Sm site in each snRNA, to form the core domain of the respective snRNP particle. Core domain formation is a prerequisite for re-import into the nucleus, where these snRNPs mature via addition of their particle-specific proteins. Here we present a crystal structure of the U4 snRNP core domain at 3.6 Å resolution, detailing how the Sm site heptad (AUUUUUG) binds inside the central hole of the heptameric ring of Sm proteins, interacting one-to-one with SmE-SmG-SmD3-SmB-SmD1-SmD2-SmF. An irregular backbone conformation of the Sm site sequence combined with the asymmetric structure of the heteromeric protein ring allows each base to interact in a distinct manner with four key residues at equivalent positions in the L3 and L5 loops of the Sm fold. A comparison of this structure with the U1 snRNP at 5.5 Å resolution reveals snRNA-dependent structural changes outside the Sm fold, which may facilitate the binding of particle-specific proteins that is crucial to biogenesis of spliceosomal snRNPs.
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DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
Evans, P
通讯作者：
Evans, P
影响因子：
64.8
作者：
Pomeranz Krummel, Daniel A;Oubridge, Chris;Leung, Adelaine K W;Li, Jade;Nagai, Kiyoshi
通讯作者：
Nagai, Kiyoshi
影响因子：
8
作者：
DIAMOND, R
通讯作者：
DIAMOND, R
影响因子：
14.9
作者：
Davis IW;Leaver-Fay A;Chen VB;Block JN;Kapral GJ;Wang X;Murray LW;Arendall WB 3rd;Snoeyink J;Richardson JS;Richardson DC
通讯作者：
Richardson DC
影响因子：
11.4
作者：
KASTNER, B;LUHRMANN, R
通讯作者：
LUHRMANN, R