SNAP output for PDB entry 7qxa [SNAP web server]

PDB-id

7qxa; SNAP-derived features in text and JSON formats; DNAproDB

Class

RNA binding protein

Method

cryo-EM (3.2 Å)

Summary

cryo-EM map of human telomerase-DNA-tpp1 complex (sharpened)

Reference

Sekne Z, Ghanim GE, van Roon AM, Nguyen THD (2022): "Structural basis of human telomerase recruitment by TPP1-POT1." Science, 375, 1173-1176. doi: 10.1126/science.abn6840.

Abstract

Telomerase maintains genome stability by extending the 3' telomeric repeats at eukaryotic chromosome ends, thereby counterbalancing progressive loss caused by incomplete genome replication. In mammals, telomerase recruitment to telomeres is mediated by TPP1, which assembles as a heterodimer with POT1. We report structures of DNA-bound telomerase in complex with TPP1 and with TPP1-POT1 at 3.2- and 3.9-angstrom resolution, respectively. Our structures define interactions between telomerase and TPP1-POT1 that are crucial for telomerase recruitment to telomeres. The presence of TPP1-POT1 stabilizes the DNA, revealing an unexpected path by which DNA exits the telomerase active site and a DNA anchor site on telomerase that is important for telomerase processivity. Our findings rationalize extensive prior genetic and biochemical findings and provide a framework for future mechanistic work on telomerase regulation.