The architecture of Tetrahymena telomerase holoenzyme

被引：96

作者：

Jiang, Jiansen ^{[1
,2
,3
]}

Miracco, Edward J. ^{[2
]}

Hong, Kyungah ^{[4
]}

Eckert, Barbara ^{[4
]}

Chan, Henry ^{[2
]}

Cash, Darian D. ^{[2
]}

Min, Bosun ^{[4
]}

Zhou, Z. Hong ^{[1
,3
]}

Collins, Kathleen ^{[4
]}

Feigon, Juli ^{[2
,3
]}

机构：

[1] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Calif Nanosyst Inst, Los Angeles, CA 90095 USA

[4] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

来源：

NATURE | 2013年 / 496卷 / 7444期

基金：

美国国家科学基金会;

关键词：

RNA-BINDING DOMAIN; STEM-LOOP IV; MOLECULAR-STRUCTURE DETERMINATION; CATALYTIC SUBUNIT TERT; N-TERMINAL DOMAIN; REVERSE-TRANSCRIPTASE; ELECTRON-MICROSCOPY; STRUCTURAL BASIS; PROTEIN P65; XPLOR-NIH;

D O I：

10.1038/nature12062

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Telomerase adds telomeric repeats to chromosome ends using an internal RNA template and a specialized telomerase reverse transcriptase (TERT), thereby maintaining genome integrity. Little is known about the physical relationships among protein and RNA subunits within a biologically functional holoenzyme. Here we describe the architecture of Tetrahymena thermophila telomerase holoenzyme determined by electron microscopy. Six of the seven proteins and the TERT-binding regions of telomerase RNA (TER) have been localized by affinity labelling. Fitting with high-resolution structures reveals the organization of TERT, TER and p65 in the ribonucleoprotein (RNP) catalytic core. p50 has an unanticipated role as a hub between the RNP catalytic core, p75-p19-p45 subcomplex, and the DNA-binding Teb1. A complete in vitro holoenzyme reconstitution assigns function to these interactions in processive telomeric repeat synthesis. These studies provide the first view of the extensive network of subunit associations necessary for telomerase holoenzyme assembly and physiological function.

引用

页码：187 / +

页数：9

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