Crystal structure of an H/ACA box ribonucleoprotein particle
Crystal structure of an H/ACA box ribonucleoprotein particle
复制标题
DOI：
10.1038/nature05151
复制
发表时间：
2006-09-21
期刊：
影响因子：
64.8
通讯作者：
Ye, Keqiong
中科院分区：
文献类型：
--
作者：
Li, Ling;Ye, Keqiong
H/ACA 核糖核蛋白颗粒 (RNP) 是 RNA 假尿苷合酶家族，可通过引导 RNA 指定修饰位点。它们还参与真核核糖体 RNA 加工，并且是脊椎动物端粒酶的组成部分。在这里，我们以 2.3 埃的分辨率报告了由蛋白质 Cbf5、Nop10、Gar1 和 L7ae 以及单发夹 H/ACA RNA 组成的整个古菌 H/ACA RNP 的晶体结构，揭示了该复合物的模块化组织。 RNA 上茎结合到由 L7ae、Nop10 和 Cbf5 形成的复合表面，RNA 下茎和 ACA 特征基序结合到 Cbf5 的 PUA 结构域，从而定位中间指导序列，以便它们与底物 RNA 配对。此外，Gar1 可以调节底物的加载和释放。该结构合理化了 H/ACA RNA 的共有结构，表明了每种蛋白质的功能作用，并为理解 RNA 引导的假尿苷化机制以及 H/ACA RNP 的各种细胞功能提供了框架。
H/ACA ribonucleoprotein particles (RNPs) are a family of RNA pseudouridine synthases that specify modification sites through guide RNAs. They also participate in eukaryotic ribosomal RNA processing and are a component of vertebrate telomerases. Here we report the crystal structure, at 2.3 angstrom resolution, of an entire archaeal H/ACA RNP consisting of proteins Cbf5, Nop10, Gar1 and L7ae, and a single-hairpin H/ACA RNA, revealing a modular organization of the complex. The RNA upper stem is bound to a composite surface formed by L7ae, Nop10 and Cbf5, and the RNA lower stem and ACA signature motif are bound to the PUA domain of Cbf5, thereby positioning middle guide sequences so that they are primed to pair with substrate RNA. Furthermore, Gar1 may regulate substrate loading and release. The structure rationalizes the consensus structure of H/ACA RNAs, suggests a functional role of each protein, and provides a framework for understanding the mechanism of RNA-guided pseudouridylation, as well as various cellular functions of H/ACA RNP.