端粒酶 RNA 识别和 RNP 组装的结构基础由全酶 La 家族蛋白 p65 完成。
Structural basis for telomerase RNA recognition and RNP assembly by the holoenzyme La family protein p65.
机构信息
Department of Chemistry, and the Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095-1569, USA.
出版信息
Mol Cell. 2012 Jul 13;47(1):16-26. doi: 10.1016/j.molcel.2012.05.018. Epub 2012 Jun 14.
Telomerase is a ribonucleoprotein complex essential for maintenance of telomere DNA at linear chromosome ends. The catalytic core of Tetrahymena telomerase comprises a ternary complex of telomerase RNA (TER), telomerase reverse transcriptase (TERT), and the essential La family protein p65. NMR and crystal structures of p65 C-terminal domain and its complex with stem IV of TER reveal that RNA recognition is achieved by a combination of single- and double-stranded RNA binding, which induces a 105° bend in TER. The domain is a cryptic, atypical RNA recognition motif with a disordered C-terminal extension that forms an α helix in the complex necessary for hierarchical assembly of TERT with p65-TER. This work provides the first structural insight into biogenesis and assembly of TER with a telomerase-specific protein. Additionally, our studies define a structurally homologous domain (xRRM) in genuine La and LARP7 proteins and suggest a general mode of RNA binding for biogenesis of their diverse RNA targets.
端粒酶是一种核糖核蛋白复合物，对于维持线性染色体末端的端粒 DNA 至关重要。四膜虫端粒酶的催化核心由端粒酶 RNA（TER）、端粒酶逆转录酶（TERT）和必需的 La 家族蛋白 p65 组成的三元复合物构成。p65 C 端结构域及其与 TER 茎 IV 复合物的 NMR 和晶体结构揭示了 RNA 识别是通过单链和双链 RNA 结合的组合来实现的，这导致 TER 发生 105°弯曲。该结构域是一种隐匿的、非典型的 RNA 识别基序，具有无规卷曲的 C 端延伸，在复合物中形成 α 螺旋，对于 TERT 与 p65-TER 的分级组装是必需的。这项工作提供了第一个关于端粒酶特异性蛋白的 TER 生物发生和组装的结构见解。此外，我们的研究在真正的 La 和 LARP7 蛋白中定义了一个结构同源的结构域（xRRM），并提出了一个用于其各种 RNA 靶标生物发生的通用 RNA 结合模式。
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