7LMB

Tetrahymena telomerase T5D5 structure at 3.8 Angstrom

7LMB の概要

• エントリーDOI: 10.2210/pdb7lmb/pdb
• 関連するPDBエントリー: 7LMA
• EMDBエントリー: 23437 23438 23439
• 分子名称: Telomerase RNA, telomere DNA, Telomerase La-related protein p65, ... (9 entities in total)
• 機能のキーワード: telomerase, polymerase, reverse transcriptase, ribonucleoprotein, replication, replication-rna-dna complex, replication/rna/dna
• 由来する生物種: Tetrahymena thermophila; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 432265.59

構造登録者

He, Y.,Wang, Y.,Liu, B.,Helmling, C.,Susac, L.,Cheng, R.,Zhou, Z.H.,Feigon, J. (登録日: 2021-02-05, 公開日: 2021-05-12, 最終更新日: 2025-05-28)

主引用文献

He, Y.,Wang, Y.,Liu, B.,Helmling, C.,Susac, L.,Cheng, R.,Zhou, Z.H.,Feigon, J.
Structures of telomerase at several steps of telomere repeat synthesis.
Nature, 593:454-459, 2021

PubMed Abstract: Telomerase is unique among the reverse transcriptases in containing a noncoding RNA (known as telomerase RNA (TER)) that includes a short template that is used for the processive synthesis of G-rich telomeric DNA repeats at the 3' ends of most eukaryotic chromosomes. Telomerase maintains genomic integrity, and its activity or dysregulation are critical determinants of human longevity, stem cell renewal and cancer progression. Previous cryo-electron microscopy structures have established the general architecture, protein components and stoichiometries of Tetrahymena and human telomerase, but our understandings of the details of DNA-protein and RNA-protein interactions and of the mechanisms and recruitment involved remain limited. Here we report cryo-electron microscopy structures of active Tetrahymena telomerase with telomeric DNA at different steps of nucleotide addition. Interactions between telomerase reverse transcriptase (TERT), TER and DNA reveal the structural basis of the determination of the 5' and 3' template boundaries, handling of the template-DNA duplex and separation of the product strand during nucleotide addition. The structure and binding interface between TERT and telomerase protein p50 (a homologue of human TPP1) define conserved interactions that are required for telomerase activation and recruitment to telomeres. Telomerase La-related protein p65 remodels several regions of TER, bridging the 5' and 3' ends and the conserved pseudoknot to facilitate assembly of the TERT-TER catalytic core.

PubMed: 33981033
DOI: 10.1038/s41586-021-03529-9

実験手法

ELECTRON MICROSCOPY (3.8 Å)