Structural and functional insights into CST tethering in Tetrahymena thermophila telomerase

Yuanyuan Ma; Chenhui Huang; Ting Tang; Bin Wu; Hongjuan Xue; Yu Cao; Jian Wu; Bingbing Wan; Ming Lei

doi:10.1016/j.str.2022.10.004

Structural and functional insights into CST tethering in Tetrahymena thermophila telomerase

Structure. 2022 Dec 1;30(12):1565-1572.e4. doi: 10.1016/j.str.2022.10.004.

Authors

Yuanyuan Ma¹, Chenhui Huang¹, Ting Tang², Bin Wu³, Hongjuan Xue³, Yu Cao⁴, Jian Wu⁵, Bingbing Wan⁶, Ming Lei⁷

Affiliations

¹ Shanghai Institute of Precision Medicine, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China.
² CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
³ National Facility for Protein Science in Shanghai, Zhangjiang Lab, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.
⁴ Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
⁵ Shanghai Institute of Precision Medicine, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China. Electronic address: wujian@shsmu.edu.cn.
⁶ Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: wanb@sjtu.edu.cn.
⁷ Shanghai Institute of Precision Medicine, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China. Electronic address: leim@shsmu.edu.cn.

PMID: 36459975
DOI: 10.1016/j.str.2022.10.004

Abstract

Telomerase is crucial for telomere maintenance and genome integrity. The most salient feature of Tetrahymena telomerase is that its CST subcomplex (p75-p45-p19) is tethered to the telomerase catalytic core by interacting with the hub p50. Although the cryoelectron microscopy (cryo-EM) structures of Tetrahymena telomerase have recently been reported, the mechanisms of how and why p50 bridges the CST subcomplex to the telomerase catalytic core remain unclear. Here, we present the nuclear magnetic resonance (NMR) structure of the p75_OB1-p50_PBM complex. Loss of the interaction between p75 and p50 detaches the CST subcomplex from the telomerase catalytic core in Tetrahymena. The tethering of the CST subcomplex to telomerase is required for telomere homeostasis. However, the detached CST subcomplex is still capable of facilitating the telomeric complementary-strand (C-strand) fill in similar to the non-tethered CST complexes in other organisms. These results expand our understanding of telomere synthesis in Tetrahymena.

Keywords: CST; Tetrahymena; p50; p75; structure; telomerase; telomere.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Catalytic Domain
Cryoelectron Microscopy
Telomerase*
Telomere
Tetrahymena thermophila*

Substances

Telomerase