+Open data
-Basic information
Entry | Database: PDB / ID: 7v9a | ||||||
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Title | biogenesis module of human telomerase holoenzyme | ||||||
Components |
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Keywords | REPLICATION / Telomerase | ||||||
Function / homology | Function and homology information 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 | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.94 Å | ||||||
Authors | Wan, F. / Ding, Y. / Yang, L. / Wu, Z. / Wu, J. / Lei, M. | ||||||
Funding support | China, 1items
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Citation | Journal: Cell Res / Year: 2021 Title: Zipper head mechanism of telomere synthesis by human telomerase. Authors: Futang Wan / Yongbo Ding / Yuebin Zhang / Zhenfang Wu / Shaobai Li / Lin Yang / Xiangyu Yan / Pengfei Lan / Guohui Li / Jian Wu / Ming Lei / Abstract: Telomerase, a multi-subunit ribonucleoprotein complex, is a unique reverse transcriptase that catalyzes the processive addition of a repeat sequence to extend the telomere end using a short fragment ...Telomerase, a multi-subunit ribonucleoprotein complex, is a unique reverse transcriptase that catalyzes the processive addition of a repeat sequence to extend the telomere end using a short fragment of its own RNA component as the template. Despite recent structural characterizations of human and Tetrahymena telomerase, it is still a mystery how telomerase repeatedly uses its RNA template to synthesize telomeric DNA. Here, we report the cryo-EM structure of human telomerase holoenzyme bound with telomeric DNA at resolutions of 3.5 Å and 3.9 Å for the catalytic core and biogenesis module, respectively. The structure reveals that a leucine residue Leu980 in telomerase reverse transcriptase (TERT) catalytic subunit functions as a zipper head to limit the length of the short primer-template duplex in the active center. Moreover, our structural and computational analyses suggest that TERT and telomerase RNA (hTR) are organized to harbor a preformed active site that can accommodate short primer-template duplex substrates for catalysis. Furthermore, our findings unveil a double-fingers architecture in TERT that ensures nucleotide addition processivity of human telomerase. We propose that the zipper head Leu980 is a structural determinant for the sequence-based pausing signal of DNA synthesis that coincides with the RNA element-based physical template boundary. Functional analyses unveil that the non-glycine zipper head plays an essential role in both telomerase repeat addition processivity and telomere length homeostasis. In addition, we also demonstrate that this zipper head mechanism is conserved in all eukaryotic telomerases. Together, our study provides an integrated model for telomerase-mediated telomere synthesis. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7v9a.cif.gz | 393.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7v9a.ent.gz | 305.3 KB | Display | PDB format |
PDBx/mmJSON format | 7v9a.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7v9a_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 7v9a_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 7v9a_validation.xml.gz | 53.3 KB | Display | |
Data in CIF | 7v9a_validation.cif.gz | 81.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/v9/7v9a ftp://data.pdbj.org/pub/pdb/validation_reports/v9/7v9a | HTTPS FTP |
-Related structure data
Related structure data | 31813MC 7v99C C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-H/ACA ribonucleoprotein complex subunit ... , 4 types, 8 molecules CGDHEIFJ
#2: Protein | Mass: 57779.211 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) References: UniProt: O60832, Isomerases; Intramolecular transferases; Transferring other groups #3: Protein | Mass: 22387.963 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9NY12 #4: Protein | Mass: 17226.070 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9NX24 #5: Protein | Mass: 7719.989 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9NPE3 |
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-Protein / RNA chain , 2 types, 2 molecules BR
#1: Protein | Mass: 59357.070 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9BUR4 |
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#6: RNA chain | Mass: 145477.797 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: GenBank: 1932797 |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Biogenesis module / Type: COMPLEX / Entity ID: all / Source: NATURAL |
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Source (natural) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.9 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 62 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.94 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 167923 / Symmetry type: POINT |