Crystal structure of human spliceosomal U1 snRNP at 5.5 A resolution.
Crystal structure of human spliceosomal U1 snRNP at 5.5 A resolution.
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DOI：
10.1038/nature07851
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发表时间：
2009-03-26
期刊：
影响因子：
64.8
通讯作者：
Nagai, Kiyoshi
中科院分区：
文献类型：
--
作者：
Pomeranz Krummel, Daniel A;Oubridge, Chris;Leung, Adelaine K W;Li, Jade;Nagai, Kiyoshi
人剪接体U1小核核糖核蛋白颗粒（snRNP）由U1小核RNA和10种蛋白质组成，识别前体信使RNA的5′剪接位点，并启动剪接体的组装以切除内含子。一个电子密度图的功能核心的U1 snRNP在5.5 μ m的分辨率，使我们能够建立的RNA，并结合位点特异性标记的个别蛋白质，将七个Sm蛋白，U1-C和U1- 70 K到地图。在这里，我们提出了一个spliceosomal snRNP的详细结构，揭示了亚基之间的复杂相互作用的层次网络。U1- 70 K的一个显著特征是其氨基端多肽从其RNA结合结构域延伸180 μ m，包裹由7个Sm蛋白组成的核心结构域，最后接触U1-C，这对5′-剪接位点识别至关重要。U1 snRNP的结构提供了对U1 snRNP组装的见解，并提出了5′-剪接位点识别的可能机制。
Human spliceosomal U1 small nuclear ribonucleoprotein particles (snRNPs), which consist of U1 small nuclear RNA and ten proteins, recognize the 5′ splice site within precursor messenger RNAs and initiate the assembly of the spliceosome for intron excision. An electron density map of the functional core of U1 snRNP at 5.5 Å resolution has enabled us to build the RNA and, in conjunction with site-specific labelling of individual proteins, to place the seven Sm proteins, U1-C and U1-70K into the map. Here we present the detailed structure of a spliceosomal snRNP, revealing a hierarchical network of intricate interactions between subunits. A striking feature is the amino (N)-terminal polypeptide of U1-70K, which extends over a distance of 180 Å from its RNA binding domain, wraps around the core domain consisting of the seven Sm proteins and finally contacts U1-C, which is crucial for 5′-splice-site recognition. The structure of U1 snRNP provides insights into U1 snRNP assembly and suggests a possible mechanism of 5′-splice-site recognition.