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

2026-03-04 REL PDBe INITIAL_RELEASE REPOSITORY INITIAL_RELEASE REPOSITORY INITIAL_RELEASE REPOSITORY INITIAL_RELEASE REPOSITORY INITIAL_RELEASE REPOSITORY INITIAL_RELEASE REPOSITORY INITIAL_RELEASE REPOSITORY INITIAL_RELEASE REPOSITORY DATABASE_REFERENCES citation citation_author em_admin _citation.country _citation.journal_abbrev _citation.journal_id_CSD _citation.journal_id_ISSN _citation.pdbx_database_id_PubMed _citation.title _citation_author.identifier_ORCID _citation_author.name _em_admin.last_update EXPERIMENTAL_SUMMARY citation citation_author em_admin _citation.country _citation.journal_abbrev _citation.journal_id_CSD _citation.journal_id_ISSN _citation.pdbx_database_id_PubMed _citation.title _citation_author.identifier_ORCID _citation_author.name _em_admin.last_update DATABASE_REFERENCES citation em_admin _citation.journal_volume _citation.page_first _citation.page_last _em_admin.last_update EXPERIMENTAL_SUMMARY citation em_admin _citation.journal_volume _citation.page_first _citation.page_last _em_admin.last_update PDBe PDBe 2025-08-28 2026-01-28 2026-01-28 2026-03-04 UK Research and Innovation (UKRI) MC_UP_1201/19 United Kingdom European Molecular Biology Organization (EMBO) Young Investigator Program Award European Union Wellcome Trust 226015/Z/22/Z United Kingdom National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) 2R35GM122579 United States Howard Hughes Medical Institute (HHMI) United States Cryo-EM structure of the catalytic core of human telomerase at the pre-termination state of the repeat addition cycle Balch S Franco-Echevarria E Ghanim GE Kretsch RC Das R Nguyen THD Yu H Ghanim GE Sigurdur TR Ding Y Das R Nguyen THD telomerase, H/ACA, RNA BINDING PROTEIN Balch S Franco-Echevarria E Ghanim GE Kretsch RC Das R Nguyen THD Structures of nucleotide-bound human telomerase at several steps of its telomeric DNA repeat addition cycle. Nat Commun UK 17 1847 1847 2026 41565648 doi:10.1038/s41467-026-68560-8 2041-1723 9si0 FULLOVERLAP EMDB EMD-54922 associated EM volume

Cryo-EM structure of the catalytic core lobe of human telomerase in the initiation state Cryo-EM structure of the catalytic core lobe of human telomerase in the initiation state 0 1 2 3 4 5 6 Homo sapiens 0.311 Histone H2A Homo sapiens 0.014140584 1 LEVO MSGRGKQGGKARAKAKTRSSRAGLQFPVGRVRRLLRKGNYAERVGAGAPVYLAAVLEYLTAEILELAGNAARDNKKTRII PRHLQLAIRNDEELNKLLGKVTIAQGGVLPNIQAVLLPKKTESHHKAKGK B2R5B3 Histone H2B Homo sapiens 0.018074932 1 LEVO MPDPAKSAPAPKKGSKKAVTKVQKKDGKKRKRSRKESYSVYVYKVLKQVHPDTGISSKAMGIMNSFVNDIFERIAGEASR LAHYNKRSTITSREIQTAVRLLLPGELAKHAVSEGTKAVTKYTSSNPRNLSPTKPGGSEDRQPPPSQLSAIPPFCLVLRA GIAGQV B4DR52 DNA (5'-D(P*GP*TP*TP*AP*GP*GP*GP*TP*TP*A)-3') Homo sapiens 0.010422683999999998 1 (DT)(DT)(DA)(DG)(DG)(DG)(DT)(DT)(DA)(DG)(DG)(DG)(DT)(DT)(DA)(DG)(DG)(DG)(DT)(DT) (DA)(DG)(DG)(DG)(DT)(DT)(DA)(DG)(DG)(DG)(DT)(DT)(DA) DNA Adrenocortical dysplasia protein homolog Homo sapiens 0.049013086 1 LEVO MAGSGRLVLRPWIRELILGSETPSSPRAGQLLEVLQDAEAAVAGPSHAPDTSDVGATLLVSDGTHSVRCLVTREALDTSD WEEKEFGFRGTEGRLLLLQDCGVHVQVAEGGAPAEFYLQVDRFSLLPTEQPRLRVPGCNQDLDVQKKLYDCLEEHLSEST SSNAGLSLSQLLDEMREDQEHQGALVCLAESCLTLEGPCTAPPVTHWAASRCKATGEAVYTVPSSMLCISENDQLILSSL GPCQRTQGPELPPPDPALQDLSLTLIASPPSSPSSSGTPALPGHMSSEESGTSISLLPALSLAAPDPGQRSSSQPSPAIC SAPATLTPRSPHASRTPSSPLQSCTPSLSPRSHVPSPHQALVTRPQKPSLEFKEFVGLPCKNRPPFPRTGATRGAQEPCS VWEPPKRHRDGSAFQYEYEPPCTSLCARVQAVRLPPQLMAWALHFLMDAQPGSEPTPM Q96AP0 hTR, human telomerase RNA Homo sapiens 0.145477797 1 GGGUUGCGGAGGGUGGGCCUGGGAGGGGUGGUGGCCAUUUUUUGUCUAACCCUAACUGAGAAGGGCGUAGGCGCCGUGCU UUUGCUCCCCGCGCGCUGUUUUUCUCGCUGACUUUCAGCGGGCGGAAAAGCCUCGGCCUGCCGCCUUCCACCGUUCAUUC UAGAGCAAACAAAAAAUGUCAGCUGCUGGCCCGUUCGCCCCUCCCGGGGACCUGCGGCGGGUCGCCUGCCCAGCCCCCGA ACCCCGCCUGGAGGCCGCGGUCGGCCCGGGGCUUCUCCGGAGGCACCCACUGCCACCGCGAAGAGUUGGGCUCUGUCAGC CGCGGGUCUCUCGGGGGCGAGGGCGAGGUUCAGGCCUUUCAGGCCGCAGGAAGAGGAACGGAGCGAGUCCCCGCGCGCGG CGCGAUUCCCUGAGCUGUGGGACGUGCACCCAGGACUCGGCUCACACAUGC U85256.1 Telomerase reverse transcriptase Homo sapiens 0.127195812 1 Homo sapiens LEVO MPRAPRCRAVRSLLRSHYREVLPLATFVRRLGPQGWRLVQRGDPAAFRALVAQCLVCVPWDARPPPAAPSFRQVSCLKEL VARVLQRLCERGAKNVLAFGFALLDGARGGPPEAFTTSVRSYLPNTVTDALRGSGAWGLLLRRVGDDVLVHLLARCALFV LVAPSCAYQVCGPPLYQLGAATQARPPPHASGPRRRLGCERAWNHSVREAGVPLGLPAPGARRRGGSASRSLPLPKRPRR GAAPEPERTPVGQGSWAHPGRTRGPSDRGFCVVSPARPAEEATSLEGALSGTRHSHPSVGRQHHAGPPSTSRPPRPWDTP CPPVYAETKHFLYSSGDKEQLRPSFLLSSLRPSLTGARRLVETIFLGSRPWMPGTPRRLPRLPQRYWQMRPLFLELLGNH AQCPYGVLLKTHCPLRAAVTPAAGVCAREKPQGSVAAPEEEDTDPRRLVQLLRQHSSPWQVYGFVRACLRRLVPPGLWGS RHNERRFLRNTKKFISLGKHAKLSLQELTWKMSVRDCAWLRRSPGVGCVPAAEHRLREEILAKFLHWLMSVYVVELLRSF FYVTETTFQKNRLFFYRKSVWSKLQSIGIRQHLKRVQLRELSEAEVRQHREARPALLTSRLRFIPKPDGLRPIVNMDYVV GARTFRREKRAERLTSRVKALFSVLNYERARRPGLLGASVLGLDDIHRAWRTFVLRVRAQDPPPELYFVKVDVTGAYDTI PQDRLTEVIASIIKPQNTYCVRRYAVVQKAAHGHVRKAFKSHVSTLTDLQPYMRQFVAHLQETSPLRDAVVIEQSSSLNE ASSGLFDVFLRFMCHHAVRIRGKSYVQCQGIPQGSILSTLLCSLCYGDMENKLFAGIRRDGLLLRLVDDFLLVTPHLTHA KTFLRTLVRGVPEYGCVVNLRKTVVNFPVEDEALGGTAFVQMPAHGLFPWCGLLLDTRTLEVQSDYSSYARTSIRASLTF NRGFKAGRNMRRKLFGVLRLKCHSLFLDLQVNSLQTVCTNIYKILLLQAYRFHACVLQLPFHQQVWKNPTFFLRVISDTA SLCYSILKAKNAGMSLGAKGAAGPLPSEAVQWLCHQAFLLKLTRHRVTYVPLLGSLRTAQTQLSRKLPGTTLTALEAAAN PALPSDFKTILD O14746 2.7.7.49 2'-deoxy-5'-O-[(R)-hydroxy{[(S)-hydroxy(phosphonooxy)phosphoryl]methyl}phosphoryl]guanosine 0.000505208 1 1GC singleParticle particle 8.0 20.0 C8H18N2O4S HEPES 150.0 NaCl Sodium Chloride 2.0 MgCl2 Magnesium Chloride 0.05 (C2H4O)nC14H22O Igepal CA630 1.0 C12H22O11 Trehalose 1.0 C4H10O2S2 DTT C-flat COPPER 400 CARBON CONTINUOUS 5.0 ETHANE 100 277 FEI VITROBOT MARK IV TFS KRIOS FLOOD BEAM BRIGHT FIELD FIELD EMISSION GUN 300 50.0 2.7 1.0 2.4 81000.0 45872.0 FEI TITAN KRIOS AUTOGRID HOLDER NITROGEN 78.0 GIF Quantum LS 20 GATAN K3 (6k x 4k) 69180 2.5 48.0 1

All images were processed using RELION 4.0, RELION 5.0 and CryoSPARC 4.1.2

14883068 CTFFIND 4 PHASE FLIPPING AND AMPLITUDE CORRECTION 3.8 FSC 0.143 CUT-OFF RELION 5.0 95317 MAXIMUM LIKELIHOOD RELION 4.0 MAXIMUM LIKELIHOOD RELION 5.0 RELION 5.0 emd_54922.map.gz 1 IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) 280 280 280 0 0 0 280 280 280 296.52002 296.52002 296.52002 90.0 90.0 90.0 X Y Z -0.013319239 0.02845817 0.00006970757 0.0008880969 1.059 1.059 1.059 0.005 AUTHOR ::::EMDATABANK.org::::EMD-54922:::: 7QXA PDB experimental model emd_54922_msk_1.map emd_54922_half_map_2.map.gz 1 IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) 280 280 280 0 0 0 280 280 280 296.52002 296.52002 296.52002 90.0 90.0 90.0 X Y Z -0.01794529 0.034244094 0.000070018854 0.001706665 1.059 1.059 1.059 AUTHOR ::::EMDATABANK.org::::EMD-54922:::: emd_54922_half_map_1.map.gz 1 IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) 280 280 280 0 0 0 280 280 280 296.52002 296.52002 296.52002 90.0 90.0 90.0 X Y Z -0.018979019 0.032932173 0.00006939623 0.0016987695 1.059 1.059 1.059 AUTHOR ::::EMDATABANK.org::::EMD-54922::::