7UY5

Tetrahymena telomerase with CST

7UY5 の概要

• エントリーDOI: 10.2210/pdb7uy5/pdb
• 関連するPDBエントリー: 7UY6 7UY7 7UY8
• EMDBエントリー: 26863 26864 26865 26866 26867 26868 26869
• 分子名称: Telomerase La-related protein p65, Telomerase-associated protein of 19 kDa, Telomerase-associated protein of 45 kDa, ... (12 entities in total)
• 機能のキーワード: telomerase, rnp, cst, replication
• 由来する生物種: Tetrahymena thermophila; 詳細
• タンパク質・核酸の鎖数: 11
• 化学式量合計: 572324.42

構造登録者

He, Y.,Song, H.,Chan, H.,Wang, Y.,Liu, B.,Susac, L.,Zhou, Z.H.,Feigon, J. (登録日: 2022-05-06, 公開日: 2022-07-13, 最終更新日: 2025-05-14)

主引用文献

He, Y.,Song, H.,Chan, H.,Liu, B.,Wang, Y.,Susac, L.,Zhou, Z.H.,Feigon, J.
Structure of Tetrahymena telomerase-bound CST with polymerase alpha-primase.
Nature, 608:813-818, 2022

PubMed Abstract: Telomeres are the physical ends of linear chromosomes. They are composed of short repeating sequences (such as TTGGGG in the G-strand for Tetrahymena thermophila) of double-stranded DNA with a single-strand 3' overhang of the G-strand and, in humans, the six shelterin proteins: TPP1, POT1, TRF1, TRF2, RAP1 and TIN2. TPP1 and POT1 associate with the 3' overhang, with POT1 binding the G-strand and TPP1 (in complex with TIN2) recruiting telomerase via interaction with telomerase reverse transcriptase (TERT). The telomere DNA ends are replicated and maintained by telomerase, for the G-strand, and subsequently DNA polymerase α-primase (PolαPrim), for the C-strand. PolαPrim activity is stimulated by the heterotrimeric complex CTC1-STN1-TEN1 (CST), but the structural basis of the recruitment of PolαPrim and CST to telomere ends remains unknown. Here we report cryo-electron microscopy (cryo-EM) structures of Tetrahymena CST in the context of the telomerase holoenzyme, in both the absence and the presence of PolαPrim, and of PolαPrim alone. Tetrahymena Ctc1 binds telomerase subunit p50, a TPP1 orthologue, on a flexible Ctc1 binding motif revealed by cryo-EM and NMR spectroscopy. The PolαPrim polymerase subunit POLA1 binds Ctc1 and Stn1, and its interface with Ctc1 forms an entry port for G-strand DNA to the POLA1 active site. We thus provide a snapshot of four key components that are required for telomeric DNA synthesis in a single active complex-telomerase-core ribonucleoprotein, p50, CST and PolαPrim-that provides insights into the recruitment of CST and PolαPrim and the handoff between G-strand and C-strand synthesis.

PubMed: 35831498
DOI: 10.1038/s41586-022-04931-7

実験手法

ELECTRON MICROSCOPY (3.5 Å)