7QXS

Cryo-EM structure of human telomerase-DNA-TPP1-POT1 complex (with POT1 side chains)

Summary for 7QXS

• Entry DOI: 10.2210/pdb7qxs/pdb
• Related: 7QXA 7QXB
• EMDB information: 14196 14197 14198 14199
• Descriptor: Telomerase reverse transcriptase, RNA (256-MER), Histone H2A, ... (7 entities in total)
• Functional Keywords: reverse transcriptase, ribonucleoprotein, telomerase, telomere, dna binding protein, rna binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 7
• Total formula weight: 434924.07

Authors

Sekne, Z.,Ghanim, G.E.,van Roon, A.M.M.,Nguyen, T.H.D. (deposition date: 2022-01-27, release date: 2022-03-02, Last modification date: 2024-11-20)

Primary citation

Sekne, Z.,Ghanim, G.E.,van Roon, A.M.,Nguyen, T.H.D.
Structural basis of human telomerase recruitment by TPP1-POT1.
Science, 375:1173-1176, 2022

PubMed 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.

PubMed: 35201900
DOI: 10.1126/science.abn6840

Experimental method

ELECTRON MICROSCOPY (3.9 Å)