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Open data
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Basic information
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Title | Human telomerase catalytic core with shelterin protein TPP1 | ||||||||||||
![]() | Telomerase catalytic core structure with shelterin protein TPP1 | ||||||||||||
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![]() | DNA / RNA / REPLICATION | ||||||||||||
Function / homology | ![]() positive regulation of single-stranded telomeric DNA binding / telomere assembly / positive regulation of hair cycle / template-free RNA nucleotidyltransferase / positive regulation of transdifferentiation / TERT-RMRP complex / DNA strand elongation / RNA-directed RNA polymerase complex / segmentation / siRNA transcription ...positive regulation of single-stranded telomeric DNA binding / telomere assembly / positive regulation of hair cycle / template-free RNA nucleotidyltransferase / positive regulation of transdifferentiation / TERT-RMRP complex / DNA strand elongation / RNA-directed RNA polymerase complex / segmentation / siRNA transcription / positive regulation of protein localization to nucleolus / urogenital system development / protection from non-homologous end joining at telomere / telomerase catalytic core complex / RNA-templated DNA biosynthetic process / : / establishment of protein localization to telomere / telomerase activity / shelterin complex / Telomere C-strand synthesis initiation / Telomere C-strand (Lagging Strand) Synthesis / positive regulation of telomere maintenance / nuclear telomere cap complex / Processive synthesis on the C-strand of the telomere / Polymerase switching on the C-strand of the telomere / Removal of the Flap Intermediate from the C-strand / siRNA processing / telomere capping / telomerase holoenzyme complex / positive regulation of vascular associated smooth muscle cell migration / telomerase RNA binding / embryonic limb morphogenesis / protein localization to chromosome, telomeric region / DNA biosynthetic process / RNA-templated transcription / telomeric DNA binding / positive regulation of stem cell proliferation / mitochondrial nucleoid / negative regulation of cellular senescence / negative regulation of telomere maintenance via telomerase / Telomere Extension By Telomerase / telomere maintenance via telomerase / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / replicative senescence / positive regulation of Wnt signaling pathway / positive regulation of G1/S transition of mitotic cell cycle / negative regulation of endothelial cell apoptotic process / response to cadmium ion / DNA polymerase binding / Packaging Of Telomere Ends / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / : / positive regulation of vascular associated smooth muscle cell proliferation / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / positive regulation of telomere maintenance via telomerase / Inhibition of DNA recombination at telomere / Meiotic synapsis / telomere maintenance / mitochondrion organization / positive regulation of nitric-oxide synthase activity / skeletal system development / positive regulation of glucose import / Formation of the beta-catenin:TCF transactivating complex / intracellular protein transport / regulation of protein stability / DNA Damage/Telomere Stress Induced Senescence / PML body / transcription coactivator binding / positive regulation of miRNA transcription / RNA-directed DNA polymerase / positive regulation of angiogenesis / RNA-directed DNA polymerase activity / positive regulation of protein binding / protein-folding chaperone binding / cellular response to hypoxia / negative regulation of neuron apoptotic process / chromosome, telomeric region / tRNA binding / nuclear body / nuclear speck / negative regulation of gene expression / RNA-dependent RNA polymerase activity / protein-containing complex binding / nucleolus / protein homodimerization activity / DNA binding / RNA binding / nucleoplasm / identical protein binding / nucleus / metal ion binding / plasma membrane / cytosol Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||||||||
![]() | Liu B / He Y | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structure of active human telomerase with telomere shelterin protein TPP1. Authors: Baocheng Liu / Yao He / Yaqiang Wang / He Song / Z Hong Zhou / Juli Feigon / ![]() Abstract: Human telomerase is a RNA-protein complex that extends the 3' end of linear chromosomes by synthesizing multiple copies of the telomeric repeat TTAGGG. Its activity is a determinant of cancer ...Human telomerase is a RNA-protein complex that extends the 3' end of linear chromosomes by synthesizing multiple copies of the telomeric repeat TTAGGG. Its activity is a determinant of cancer progression, stem cell renewal and cellular aging. Telomerase is recruited to telomeres and activated for telomere repeat synthesis by the telomere shelterin protein TPP1. Human telomerase has a bilobal structure with a catalytic core ribonuclear protein and a H and ACA box ribonuclear protein. Here we report cryo-electron microscopy structures of human telomerase catalytic core of telomerase reverse transcriptase (TERT) and telomerase RNA (TER (also known as hTR)), and of telomerase with the shelterin protein TPP1. TPP1 forms a structured interface with the TERT-unique telomerase essential N-terminal domain (TEN) and the telomerase RAP motif (TRAP) that are unique to TERT, and conformational dynamics of TEN-TRAP are damped upon TPP1 binding, defining the requirements for recruitment and activation. The structures further reveal that the elements of TERT and TER that are involved in template and telomeric DNA handling-including the TEN domain and the TRAP-thumb helix channel-are largely structurally homologous to those in Tetrahymena telomerase, and provide unique insights into the mechanism of telomerase activity. The binding site of the telomerase inhibitor BIBR1532 overlaps a critical interaction between the TER pseudoknot and the TERT thumb domain. Numerous mutations leading to telomeropathies are located at the TERT-TER and TEN-TRAP-TPP1 interfaces, highlighting the importance of TER-TERT and TPP1 interactions for telomerase activity, recruitment and as drug targets. | ||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 13.9 KB 13.9 KB | Display Display | ![]() |
Images | ![]() | 65.6 KB | ||
Filedesc metadata | ![]() | 6.4 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 529.1 KB | Display | ![]() |
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Full document | ![]() | 528.7 KB | Display | |
Data in XML | ![]() | 6 KB | Display | |
Data in CIF | ![]() | 6.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7treMC ![]() 7trcC ![]() 7trdC ![]() 7trfC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Telomerase catalytic core structure with shelterin protein TPP1 | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : active human telomerase RNP with shelterin protein TPP1
Entire | Name: active human telomerase RNP with shelterin protein TPP1 |
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Components |
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-Supramolecule #1: active human telomerase RNP with shelterin protein TPP1
Supramolecule | Name: active human telomerase RNP with shelterin protein TPP1 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Telomerase RNA, partial sequence
Macromolecule | Name: Telomerase RNA, partial sequence / type: rna / ID: 1 / Number of copies: 1 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 145.477797 KDa |
Sequence | String: GGGUUGCGGA GGGUGGGCCU GGGAGGGGUG GUGGCCAUUU UUUGUCUAAC CCUAACUGAG AAGGGCGUAG GCGCCGUGCU UUUGCUCCC CGCGCGCUGU UUUUCUCGCU GACUUUCAGC GGGCGGAAAA GCCUCGGCCU GCCGCCUUCC ACCGUUCAUU C UAGAGCAA ...String: GGGUUGCGGA GGGUGGGCCU GGGAGGGGUG GUGGCCAUUU UUUGUCUAAC CCUAACUGAG AAGGGCGUAG GCGCCGUGCU UUUGCUCCC CGCGCGCUGU UUUUCUCGCU GACUUUCAGC GGGCGGAAAA GCCUCGGCCU GCCGCCUUCC ACCGUUCAUU C UAGAGCAA ACAAAAAAUG UCAGCUGCUG GCCCGUUCGC CCCUCCCGGG GACCUGCGGC GGGUCGCCUG CCCAGCCCCC GA ACCCCGC CUGGAGGCCG CGGUCGGCCC GGGGCUUCUC CGGAGGCACC CACUGCCACC GCGAAGAGUU GGGCUCUGUC AGC CGCGGG UCUCUCGGGG GCGAGGGCGA GGUUCAGGCC UUUCAGGCCG CAGGAAGAGG AACGGAGCGA GUCCCCGCGC GCGG CGCGA UUCCCUGAGC UGUGGGACGU GCACCCAGGA CUCGGCUCAC ACAUGC GENBANK: GENBANK: U85256.1 |
-Macromolecule #2: Telomerase reverse transcriptase
Macromolecule | Name: Telomerase reverse transcriptase / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO / EC number: RNA-directed DNA polymerase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 130.711492 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: GHMSAWSHPQ FEKGGGSGGG SGGSAWSHPQ FEKSAMPRAP RCRAVRSLLR SHYREVLPLA TFVRRLGPQG WRLVQRGDPA AFRALVAQC LVCVPWDARP PPAAPSFRQV SCLKELVARV LQRLCERGAK NVLAFGFALL DGARGGPPEA FTTSVRSYLP N TVTDALRG ...String: GHMSAWSHPQ FEKGGGSGGG SGGSAWSHPQ FEKSAMPRAP RCRAVRSLLR SHYREVLPLA TFVRRLGPQG WRLVQRGDPA AFRALVAQC LVCVPWDARP PPAAPSFRQV SCLKELVARV LQRLCERGAK NVLAFGFALL DGARGGPPEA FTTSVRSYLP N TVTDALRG SGAWGLLLRR VGDDVLVHLL ARCALFVLVA PSCAYQVCGP PLYQLGAATQ ARPPPHASGP RRRLGCERAW NH SVREAGV PLGLPAPGAR RRGGSASRSL PLPKRPRRGA APEPERTPVG QGSWAHPGRT RGPSDRGFCV VSPARPAEEA TSL EGALSG TRHSHPSVGR QHHAGPPSTS RPPRPWDTPC PPVYAETKHF LYSSGDKEQL RPSFLLSSLR PSLTGARRLV ETIF LGSRP WMPGTPRRLP RLPQRYWQMR PLFLELLGNH AQCPYGVLLK THCPLRAAVT PAAGVCAREK PQGSVAAPEE EDTDP RRLV QLLRQHSSPW QVYGFVRACL RRLVPPGLWG SRHNERRFLR NTKKFISLGK HAKLSLQELT WKMSVRDCAW LRRSPG VGC VPAAEHRLRE EILAKFLHWL MSVYVVELLR SFFYVTETTF QKNRLFFYRK SVWSKLQSIG IRQHLKRVQL RELSEAE VR QHREARPALL TSRLRFIPKP DGLRPIVNMD YVVGARTFRR EKRAERLTSR VKALFSVLNY ERARRPGLLG ASVLGLDD I HRAWRTFVLR VRAQDPPPEL YFVKVDVTGA YDTIPQDRLT EVIASIIKPQ NTYCVRRYAV VQKAAHGHVR KAFKSHVST LTDLQPYMRQ FVAHLQETSP LRDAVVIEQS SSLNEASSGL FDVFLRFMCH HAVRIRGKSY VQCQGIPQGS ILSTLLCSLC YGDMENKLF AGIRRDGLLL RLVDDFLLVT PHLTHAKTFL RTLVRGVPEY GCVVNLRKTV VNFPVEDEAL GGTAFVQMPA H GLFPWCGL LLDTRTLEVQ SDYSSYARTS IRASLTFNRG FKAGRNMRRK LFGVLRLKCH SLFLDLQVNS LQTVCTNIYK IL LLQAYRF HACVLQLPFH QQVWKNPTFF LRVISDTASL CYSILKAKNA GMSLGAKGAA GPLPSEAVQW LCHQAFLLKL TRH RVTYVP LLGSLRTAQT QLSRKLPGTT LTALEAAANP ALPSDFKTIL D UniProtKB: Telomerase reverse transcriptase |
-Macromolecule #4: Adrenocortical dysplasia protein homolog
Macromolecule | Name: Adrenocortical dysplasia protein homolog / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 17.672637 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: GAGSGRLVLR PWIRELILGS ETPSSPRAGQ LLEVLQDAEA AVAGPSHAPD TSDVGATLLV SDGTHSVRCL VTREALDTSD WEEKEFGFR GTEGRLLLLQ DCGVHVQVAE GGAPAEFYLQ VDRFSLLPTE QPRLRVPGCN QDLDVQKKLY DCLEEHLSES T SSN UniProtKB: Adrenocortical dysplasia protein homolog |
-Macromolecule #3: Telomeric repeat substrate
Macromolecule | Name: Telomeric repeat substrate / type: dna / ID: 3 / Number of copies: 1 / Classification: DNA |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 5.514567 KDa |
Sequence | String: (DT)(DT)(DT)(DT)(DT)(DT)(DT)(DT)(DT)(DT) (DT)(DT)(DT)(DT)(DA)(DG)(DG)(DG) |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 55.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Nominal defocus max: 4.0 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: EMDB MAP EMDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 118845 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |