Telomerase is a DNA polymerase that extends the 3' ends of chromosomes by processively synthesizing multiple telomeric repeats. It is a unique ribonucleoprotein (RNP) containing a specialized telomerase reverse transcriptase (TERT) and telomerase RNA (TER) with its own template and other elements required with TERT for activity (catalytic core), as well as species-specific TER-binding proteins important for biogenesis and assembly (core RNP); other proteins bind telomerase transiently or constitutively to allow association of telomerase and other proteins with telomere ends for regulation of DNA synthesis. Here we describe how nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography of TER and protein domains helped define the structure and function of the core RNP, laying the groundwork for interpreting negative-stain and cryo electron microscopy (cryo-EM) density maps of Tetrahymena thermophila and human telomerase holoenzymes. As the resolution has improved from ∼30 Å to ∼5 Å, these studies have provided increasingly detailed information on telomerase architecture and mechanism.

中文翻译：

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端粒酶的结构生物学。

端粒酶是一种 DNA 聚合酶，通过逐步合成多个端粒重复序列来延伸染色体的 3' 端。它是一种独特的核糖核蛋白 (RNP)，包含专门的端粒酶逆转录酶 (TERT) 和端粒酶 RNA (TER) 及其自身的模板和 TERT 活性所需的其他元素（催化核心），以及物种特异性的 TER 结合蛋白对生物发生和组装很重要（核心 RNP）；其他蛋白质瞬时或组成性地结合端粒酶，使端粒酶和其他蛋白质与端粒末端结合以调节 DNA 合成。在这里，我们描述了核磁共振 (NMR) 光谱和 TER 和蛋白质域的 X 射线晶体学如何帮助定义核心 RNP 的结构和功能，为解释嗜热四膜虫和人类端粒酶全酶的负染色和冷冻电子显微镜 (cryo-EM) 密度图奠定基础。随着分辨率从~30 Å 提高到~5 Å，这些研究提供了越来越详细的端粒酶结构和机制信息。