Crystal structure of the essential N-terminal domain of telomerase reverse transcriptase
Crystal structure of the essential N-terminal domain of telomerase reverse transcriptase
复制标题
DOI：
10.1038/nsmb1054
复制
发表时间：
2006-03-01
影响因子：
16.8
通讯作者：
Cech, TR
中科院分区：
文献类型：
--
作者：
Jacobs, SA;Podell, ER;Cech, TR
端粒酶是一种核糖核蛋白酶，它将端粒DNA重复序列添加到线性染色体的末端。在这里，我们报道了端粒酶逆转录酶的任何部分的高分辨率结构，端粒酶必需n端（TEN）结构域来自嗜热四膜虫。该结构似乎代表了一种新的蛋白质折叠，在其表面的凹槽中显示了系统发育上保守的氨基酸残基。这些残基对端粒酶的催化活性至关重要，其中一些是单链端粒DNA引物序列特异性结合所必需的。带正电的C端在与其他大分子相互作用时变得有序，以非序列特异性的方式参与RNA的结合。TEN结构域结合RNA和端粒DNA的能力，加上对单表面残基诱变活性的显著强烈影响，表明该结构域如何参与端粒酶催化。
Telomerase, a ribonucleoprotein enzyme, adds telomeric DNA repeats to the ends of linear chromosomes. Here we report the first high-resolution structure of any portion of the telomerase reverse transcriptase, the telomerase essential N-terminal ( TEN) domain from Tetrahymena thermophila. The structure, which seems to represent a novel protein fold, shows phylogenetically conserved amino acid residues in a groove on its surface. These residues are crucial for telomerase catalytic activity, and several of them are required for sequence-specific binding of a single-stranded telomeric DNA primer. The positively charged C terminus, which becomes ordered upon interaction with other macromolecules, is involved in binding RNA in a non-sequence-specific manner. The TEN domain's ability to bind both RNA and telomeric DNA, coupled with the notably strong effects on activity upon mutagenesis of single surface residues, suggest how this domain contributes to telomerase catalysis.