9QAZ

Catalytic core 2 of dimeric human telomerase

Summary for 9QAZ

• Entry DOI: 10.2210/pdb9qaz/pdb
• EMDB information: 52980
• Descriptor: Telomerase reverse transcriptase, hTR, human telomerase RNA (253-mer), Histone H2A, ... (6 entities in total)
• Functional Keywords: human telomerase catalytic core, reverse transcriptase, dna substrate bound, dna binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 356095.67

Authors

Balch, S.,Sekne, Z.,Franco-Echevarria, E.,Ludzia, P.,Kretsch, R.C.,Sun, W.,Yu, H.,Ghanim, G.E.,Sigurdur, T.R.,Ding, Y.,Das, R.,Nguyen, T.H.D. (deposition date: 2025-02-28, release date: 2025-07-16, Last modification date: 2025-07-23)

Primary citation

Balch, S.,Sekne, Z.,Franco-Echevarria, E.,Ludzia, P.,Kretsch, R.C.,Sun, W.,Yu, H.,Ghanim, G.E.,Thorkelsson, S.,Ding, Y.,Das, R.,Nguyen, T.H.D.
Cryo-EM structure of human telomerase dimer reveals H/ACA RNP-mediated dimerization.
Science, 389:eadr5817-eadr5817, 2025

PubMed Abstract: Telomerase ribonucleoprotein (RNP) synthesizes telomeric repeats at chromosome ends using a telomerase reverse transcriptase (TERT) and a telomerase RNA (hTR in humans). Previous structural work showed that human telomerase is typically monomeric, containing a single copy of TERT and hTR. Evidence for dimeric complexes exists, although the composition, high-resolution structure, and function remain elusive. Here, we report the cryo-electron microscopy (cryo-EM) structure of a human telomerase dimer bound to telomeric DNA. The structure reveals a 26-subunit assembly and a dimerization interface mediated by the Hinge and ACA box (H/ACA) RNP of telomerase. Premature aging disease mutations map to this interface. Disrupting dimer formation affects RNP assembly, bulk telomerase activity, and telomere maintenance in cells. Our findings address a long-standing enigma surrounding the telomerase dimer and suggest a role for the dimer in telomerase assembly.

PubMed: 40638752
DOI: 10.1126/science.adr5817

Experimental method

ELECTRON MICROSCOPY (3.6 Å)