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Open data
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Basic information
Entry | Database: PDB / ID: 7trc | ||||||||||||
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Title | Human telomerase H/ACA RNP at 3.3 Angstrom | ||||||||||||
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![]() | REPLICATION / DNA / RNA | ||||||||||||
Function / homology | ![]() telomere formation via telomerase / box H/ACA scaRNP complex / box H/ACA telomerase RNP complex / telomerase RNA localization to Cajal body / protein localization to Cajal body / snoRNA guided rRNA pseudouridine synthesis / box H/ACA snoRNP complex / Isomerases; Intramolecular transferases; Transferring other groups / rRNA pseudouridine synthesis / box H/ACA sno(s)RNA 3'-end processing ...telomere formation via telomerase / box H/ACA scaRNP complex / box H/ACA telomerase RNP complex / telomerase RNA localization to Cajal body / protein localization to Cajal body / snoRNA guided rRNA pseudouridine synthesis / box H/ACA snoRNP complex / Isomerases; Intramolecular transferases; Transferring other groups / rRNA pseudouridine synthesis / box H/ACA sno(s)RNA 3'-end processing / pseudouridine synthesis / snRNA pseudouridine synthesis / enzyme-directed rRNA pseudouridine synthesis / telomerase RNA stabilization / Cajal body organization / box H/ACA snoRNA binding / telomerase activity / regulation of telomerase RNA localization to Cajal body / mRNA pseudouridine synthesis / pseudouridine synthase activity / scaRNA localization to Cajal body / positive regulation of establishment of protein localization to telomere / positive regulation of protein localization to Cajal body / positive regulation of telomerase RNA localization to Cajal body / sno(s)RNA-containing ribonucleoprotein complex / Telomere Extension By Telomerase / telomerase holoenzyme complex / telomerase RNA binding / rRNA modification in the nucleus and cytosol / positive regulation of double-strand break repair / Cajal body / positive regulation of double-strand break repair via nonhomologous end joining / Association of TriC/CCT with target proteins during biosynthesis / : / RNA folding / telomere maintenance via telomerase / positive regulation of double-strand break repair via homologous recombination / positive regulation of DNA repair / RNA processing / positive regulation of telomere maintenance via telomerase / fibrillar center / rRNA processing / site of double-strand break / protein-folding chaperone binding / histone binding / chromosome, telomeric region / nuclear body / DNA repair / ubiquitin protein ligase binding / protein-containing complex binding / nucleolus / RNA binding / nucleoplasm / identical protein binding / nucleus / cytoplasm / cytosol Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||||||||
![]() | Liu, B. / He, Y. / Wang, Y. / Song, H. / Zhou, Z.H. / Feigon, J. | ||||||||||||
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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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PDBx/mmCIF format | ![]() | 353.6 KB | Display | ![]() |
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PDB format | ![]() | 269 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 26085MC ![]() 7trdC ![]() 7treC ![]() 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
-H/ACA ribonucleoprotein complex subunit ... , 4 types, 8 molecules GCJFHDIE
#2: Protein | Mass: 57779.211 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: O60832, Isomerases; Intramolecular transferases; Transferring other groups #3: Protein | Mass: 7719.989 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #5: Protein | Mass: 22387.963 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #6: Protein | Mass: 17226.070 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Protein / RNA chain , 2 types, 2 molecules KB
#1: Protein | Mass: 59357.070 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#4: RNA chain | Mass: 145477.797 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: human telomerase H/ACA RNP / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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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: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 256859 / Symmetry type: POINT | ||||||||||||||||||||||||
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