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

PDB-id

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

Class

RNA binding protein

Method

cryo-EM (3.91 Å)

Summary

cryo-EM structure of human telomerase-DNA-tpp1-pot1 complex (with pot1 side chains)

Reference

Sekne Z, Ghanim GE, van Roon AM, Nguyen THD (2022): "Structural basis of human telomerase recruitment by TPP1-POT1." Science, eabn6840. 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 Å and 3.9 Å 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 DNA path exiting telomerase active site and a DNA anchor site on telomerase important for telomerase processivity. Our findings rationalize extensive prior genetic and biochemical findings and provide a framework for future mechanistic work on telomerase regulation.