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Open data
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Basic information
Entry | Database: PDB / ID: 7tre | ||||||||||||
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Title | Human telomerase catalytic core with shelterin protein TPP1 | ||||||||||||
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![]() | REPLICATION / DNA / RNA | ||||||||||||
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 / positive regulation of protein localization to nucleolus ...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 / positive regulation of protein localization to nucleolus / urogenital system development / siRNA transcription / telomerase catalytic core complex / telomerase activity / protection from non-homologous end joining at telomere / Regulation of MITF-M-dependent genes involved in DNA damage repair and senescence / : / RNA-templated DNA biosynthetic process / establishment of protein localization to telomere / 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 / siRNA processing / Polymerase switching on the C-strand of the telomere / Removal of the Flap Intermediate from the C-strand / telomere capping / positive regulation of vascular associated smooth muscle cell migration / telomerase holoenzyme complex / telomerase RNA binding / embryonic limb morphogenesis / protein localization to chromosome, telomeric region / telomeric DNA binding / DNA biosynthetic process / RNA-templated transcription / 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 / positive regulation of Wnt signaling pathway / replicative senescence / 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 / positive regulation of telomere maintenance via telomerase / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / 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 / intracellular protein transport / Formation of the beta-catenin:TCF transactivating complex / regulation of protein stability / PML body / DNA Damage/Telomere Stress Induced Senescence / 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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||||||||
![]() | Liu, B. / He, Y. / Wang, Y. / Song, H. / Zhou, Z.H. / Feigon, J. | ||||||||||||
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. | ||||||||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 320.3 KB | Display | ![]() |
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PDB format | ![]() | 237.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 26087MC ![]() 7trcC ![]() 7trdC ![]() 7trfC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: RNA chain | Mass: 145477.797 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#2: Protein | Mass: 130711.492 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#3: DNA chain | Mass: 5514.567 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
#4: Protein | Mass: 17672.637 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: active human telomerase RNP with shelterin protein TPP1 Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 4000 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 55 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 118845 / Symmetry type: POINT | ||||||||||||||||||||||||
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