Crystal structure of a Cbf5-Nop10-Gar1 complex and implications in RNA-guided pseudouridylation and dyskeratosis congenita
Crystal structure of a Cbf5-Nop10-Gar1 complex and implications in RNA-guided pseudouridylation and dyskeratosis congenita
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DOI：
10.1016/j.molcel.2005.11.017
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发表时间：
2006-01-20
期刊：
影响因子：
16
通讯作者：
Hong, L
中科院分区：
文献类型：
--
作者：
Rashid, R;Liang, B;Hong, L
H/ACA RNA-蛋白质复合物由四种蛋白质和H/ACA引导RNA组成，修饰核糖体和小核RNA。H/ACA蛋白也是哺乳动物端粒酶的重要组成部分。Cbf 5是催化靶RNA中尿苷异构化为假尿苷的H/ACA蛋白。人Cbf 5（dyskerin）突变导致先天性角化不良。在这里，我们描述了一个特定的复合物的三个古细菌H/ACA蛋白，Cbf 5，Nop 10，和Gar 1的2.1埃晶体结构。Cbf 5显示出在已知的假尿苷酰化酶中独特的结构特性，并且与其在RNA引导的假尿苷酰化中的独特功能一致。我们还描述了以前未知的结构都Nop 10和Gar 1和结构的基础上，他们在pseudouridylation的重要作用。通过使用相关结构的信息，我们已经模拟了整个核糖核蛋白复合物，包括指导和底物RNA。我们还确定了一个先天性角化不良突变簇内的一个模型dyskerin结构的网站。
H/ACA RNA-protein complexes, comprised of four proteins and an H/ACA guide RNA, modify ribosomal and small nuclear RNAs. The H/ACA proteins are also essential components of telomerase in mammals. Cbf5 is the H/ACA protein that catalyzes isomerization of uridine to pseudouridine in target RNAs. Mutations in human Cbf5 (dyskerin) lead to dyskeratosis congenita. Here, we describe the 2.1 angstrom crystal structure of a specific complex of three archaeal H/ACA proteins, Cbf5, Nop10, and Gar1. Cbf5 displays structural properties that are unique among known pseudouridine synthases and are consistent with its distinct function in RNA-guided pseudouridylation. We also describe the previously unknown structures of both Nop10 and Gar1 and the structural basis for their essential roles in pseudouridylation. By using information from related structures, we have modeled the entire ribonucleoprotein complex including both guide and substrate RNAs. We have also identified a dyskeratosis congenita mutation cluster site within a modeled dyskerin structure.