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- EMDB-7518: The catalytic core of the cryo-EM structure of substrate-bound hu... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-7518 | |||||||||
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Title | The catalytic core of the cryo-EM structure of substrate-bound human telomerase holoenzyme | |||||||||
![]() | Map of the telomerase catalytic core | |||||||||
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Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 7.7 Å | |||||||||
![]() | Nguyen THD / Tam J / Wu RA / Greber BJ / Toso D / Nogales E / Collins K | |||||||||
![]() | ![]() Title: Cryo-EM structure of substrate-bound human telomerase holoenzyme. Authors: Thi Hoang Duong Nguyen / Jane Tam / Robert A Wu / Basil J Greber / Daniel Toso / Eva Nogales / Kathleen Collins / ![]() Abstract: The enzyme telomerase adds telomeric repeats to chromosome ends to balance the loss of telomeres during genome replication. Telomerase regulation has been implicated in cancer, other human diseases, ...The enzyme telomerase adds telomeric repeats to chromosome ends to balance the loss of telomeres during genome replication. Telomerase regulation has been implicated in cancer, other human diseases, and ageing, but progress towards clinical manipulation of telomerase has been hampered by the lack of structural data. Here we present the cryo-electron microscopy structure of the substrate-bound human telomerase holoenzyme at subnanometre resolution, showing two flexibly RNA-tethered lobes: the catalytic core with telomerase reverse transcriptase (TERT) and conserved motifs of telomerase RNA (hTR), and an H/ACA ribonucleoprotein (RNP). In the catalytic core, RNA encircles TERT, adopting a well-ordered tertiary structure with surprisingly limited protein-RNA interactions. The H/ACA RNP lobe comprises two sets of heterotetrameric H/ACA proteins and one Cajal body protein, TCAB1, representing a pioneering structure of a large eukaryotic family of ribosome and spliceosome biogenesis factors. Our findings provide a structural framework for understanding human telomerase disease mutations and represent an important step towards telomerase-related clinical therapeutics. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 225.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 10.6 KB 10.6 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 14.3 KB | Display | ![]() |
Images | ![]() | 105.2 KB | ||
Masks | ![]() | 244.1 MB | ![]() | |
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 78.6 KB | Display | ![]() |
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Full document | ![]() | 77.7 KB | Display | |
Data in XML | ![]() | 494 B | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
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Links
EMDB pages | ![]() ![]() |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Map of the telomerase catalytic core | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.15 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | ![]() | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Human telomerase holoenzyme in complex with DNA substrate
Entire | Name: Human telomerase holoenzyme in complex with DNA substrate |
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Components |
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-Supramolecule #1: Human telomerase holoenzyme in complex with DNA substrate
Supramolecule | Name: Human telomerase holoenzyme in complex with DNA substrate type: complex / ID: 1 / Parent: 0 / Details: Sample was purified from human cells |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-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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Grid | Support film - Material: CARBON / Support film - topology: CONTINUOUS / Pretreatment - Type: GLOW DISCHARGE / Details: unspecified |
Vitrification | Cryogen name: ETHANE-PROPANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Number real images: 11654 / Average electron dose: 42.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Protocol: RIGID BODY FIT |
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