9SI0

Cryo-EM structure of the catalytic core of human telomerase at the pre-termination state of the repeat addition cycle

9SI0 の概要

• エントリーDOI: 10.2210/pdb9si0/pdb
• EMDBエントリー: 54922
• 分子名称: Histone H2A, Histone H2B, DNA (5'-D(P*GP*TP*TP*AP*GP*GP*GP*TP*TP*A)-3'), ... (7 entities in total)
• 機能のキーワード: telomerase, h/aca, rna binding protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 364830.10

構造登録者

Balch, S.,Franco-Echevarria, E.,Ghanim, G.E.,Kretsch, R.C.,Das, R.,Nguyen, T.H.D. (登録日: 2025-08-28, 公開日: 2026-01-28, 最終更新日: 2026-02-04)

主引用文献

Balch, S.,Franco-Echevarria, E.,Ghanim, G.E.,Kretsch, R.C.,Das, R.,Nguyen, T.H.D.
Structures of nucleotide-bound human telomerase at several steps of its telomeric DNA repeat addition cycle.
Nat Commun, 2026

PubMed Abstract: In most eukaryotes, the reverse transcriptase telomerase counteracts telomere shortening by processively adding telomeric DNA repeat sequences to chromosome ends. Telomerase activity depends on the telomerase reverse transcriptase (TERT) and the telomerase RNA (hTR in humans). Processive telomere elongation is critical for genome stability, and defects in this mechanism are linked to cellular dysfunction and human disease. However, the structural basis for telomerase repeat addition processivity in humans has remained elusive. Here, we present cryo-electron microscopy structures of human telomerase bound to telomeric DNA and an incoming nucleotide, captured at three distinct stages of its repeat addition cycle: initiation, elongation, and pre-termination. Across these states, the TERT active site maintains a conserved architecture that stabilises a short DNA-RNA duplex of constant length of four base-pairs. Beyond the active site, we identify dynamic structural features in both TERT and hTR that facilitate substrate engagement and RNA template repositioning, thereby supporting the synthesis of successive telomeric repeats. Together, these structures provide key insights into how human telomerase achieves its unique processivity to maintain telomere length and genome integrity.

PubMed: 41565648
DOI: 10.1038/s41467-026-68560-8

実験手法

ELECTRON MICROSCOPY (3.8 Å)