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端粒酶结构生物学崭露头角。

Telomerase structural biology comes of age.

机构信息

Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA 90095-1569, USA; Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA.

Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA 90095-1569, USA.

出版信息

Curr Opin Struct Biol. 2022 Oct;76:102446. doi: 10.1016/j.sbi.2022.102446. Epub 2022 Sep 6.

DOI:10.1016/j.sbi.2022.102446
PMID:36081246
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9884118/
Abstract

Telomerase is an RNA-protein complex comprising telomerase reverse transcriptase, a non-coding telomerase RNA, and proteins involved in biogenesis, assembly, localization, or recruitment. Telomerase synthesizes the telomeric DNA at the 3'-ends of linear chromosomes. During the past decade, structural studies have defined the architecture of Tetrahymena and human telomerase as well as protein and RNA domain structures, but high-resolution details of interactions remained largely elusive. In the past two years, several sub-4 Å cryo-electron microscopy structures of telomerase were published, including Tetrahymena telomerase at different steps of telomere repeat addition and human telomerase with telomere shelterin proteins that recruit telomerase to telomeres. These and other recent structural studies have expanded our understanding of telomerase assembly, mechanism, recruitment, and mutations leading to disease.

摘要

端粒酶是一种 RNA-蛋白复合物,由端粒酶逆转录酶、非编码端粒酶 RNA 和参与生物发生、组装、定位或募集的蛋白质组成。端粒酶在线性染色体的 3'末端合成端粒 DNA。在过去的十年中,结构研究已经定义了四膜虫和人端粒酶的结构以及蛋白质和 RNA 结构域结构,但相互作用的高分辨率细节在很大程度上仍然难以捉摸。在过去的两年中,发表了几个亚 4 Å 的端粒酶冷冻电子显微镜结构,包括处于端粒重复添加不同步骤的四膜虫端粒酶和与招募端粒酶到端粒的端粒庇护蛋白结合的人端粒酶。这些和其他最近的结构研究扩展了我们对端粒酶组装、机制、募集和导致疾病的突变的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/347f/9884118/f05006071ba8/nihms-1867636-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/347f/9884118/0da9d44399a0/nihms-1867636-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/347f/9884118/ed1a707ce406/nihms-1867636-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/347f/9884118/cde36ab2968b/nihms-1867636-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/347f/9884118/f05006071ba8/nihms-1867636-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/347f/9884118/0da9d44399a0/nihms-1867636-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/347f/9884118/ed1a707ce406/nihms-1867636-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/347f/9884118/cde36ab2968b/nihms-1867636-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/347f/9884118/f05006071ba8/nihms-1867636-f0004.jpg

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本文引用的文献

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Structure of active human telomerase with telomere shelterin protein TPP1.活性人端粒酶与端粒保护蛋白 TPP1 的结构。
Nature. 2022 Apr;604(7906):578-583. doi: 10.1038/s41586-022-04582-8. Epub 2022 Apr 13.
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Structural basis of RNA conformational switching in the transcriptional regulator 7SK RNP.转录调控因子 7SK RNP 中 RNA 构象转换的结构基础。
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The methyl phosphate capping enzyme Bmc1/Bin3 is a stable component of the fission yeast telomerase holoenzyme.
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Telomere C-Strand Fill-In Machinery: New Insights into the Human CST-DNA Polymerase Alpha-Primase Structures and Functions.端粒 C 链填充机制:人类 CST-DNA 聚合酶 α-引发酶结构与功能的新见解。
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Telomerase RNA structural heterogeneity in living human cells detected by DMS-MaPseq.通过DMS-MaPseq检测活的人类细胞中的端粒酶RNA结构异质性。
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Models for human telomere C-strand fill-in by CST-Polα-primase.CST-Polα-primase 对人端粒 C 链填充的模型。
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Genes Dev. 2023 Jul 1;37(13-14):555-569. doi: 10.1101/gad.350479.123. Epub 2023 Jul 26.
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