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- EMDB-17191: The H/ACA RNP lobe of human telomerase with the dyskerin thumb lo... -
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Open data
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Basic information
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Title | The H/ACA RNP lobe of human telomerase with the dyskerin thumb loop in an open conformation | ||||||||||||
![]() | Final post-processed sharpened map. | ||||||||||||
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![]() | telomerase / H/ACA / pseudouridylation / ribonucleoprotein / RNA BINDING PROTEIN | ||||||||||||
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 | single particle reconstruction / cryo EM / Resolution: 3.1 Å | ||||||||||||
![]() | Ghanim GE / Sekne Z / van Roon AMM / Balch S / Nguyen THD | ||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: 2.7 Å cryo-EM structure of human telomerase H/ACA ribonucleoprotein. Authors: George E Ghanim / Zala Sekne / Sebastian Balch / Anne-Marie M van Roon / Thi Hoang Duong Nguyen / ![]() Abstract: Telomerase is a ribonucleoprotein (RNP) enzyme that extends telomeric repeats at eukaryotic chromosome ends to counterbalance telomere loss caused by incomplete genome replication. Human telomerase ...Telomerase is a ribonucleoprotein (RNP) enzyme that extends telomeric repeats at eukaryotic chromosome ends to counterbalance telomere loss caused by incomplete genome replication. Human telomerase is comprised of two distinct functional lobes tethered by telomerase RNA (hTR): a catalytic core, responsible for DNA extension; and a Hinge and ACA (H/ACA) box RNP, responsible for telomerase biogenesis. H/ACA RNPs also have a general role in pseudouridylation of spliceosomal and ribosomal RNAs, which is critical for the biogenesis of the spliceosome and ribosome. Much of our structural understanding of eukaryotic H/ACA RNPs comes from structures of the human telomerase H/ACA RNP. Here we report a 2.7 Å cryo-electron microscopy structure of the telomerase H/ACA RNP. The significant improvement in resolution over previous 3.3 Å to 8.2 Å structures allows us to uncover new molecular interactions within the H/ACA RNP. Many disease mutations are mapped to these interaction sites. The structure also reveals unprecedented insights into a region critical for pseudouridylation in canonical H/ACA RNPs. Together, our work advances understanding of telomerase-related disease mutations and the mechanism of pseudouridylation by eukaryotic H/ACA RNPs. | ||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 77.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 29.6 KB 29.6 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10 KB | Display | ![]() |
Images | ![]() | 67.6 KB | ||
Filedesc metadata | ![]() | 8.3 KB | ||
Others | ![]() ![]() ![]() | 65.4 MB 65.7 MB 65.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8oufMC ![]() 8oueC 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 | Final post-processed sharpened map. | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.059 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Final unsharped map.
File | emd_17191_additional_1.map | ||||||||||||
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Annotation | Final unsharped map. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half-map2 resulting from gold standard refinement in RELION.
File | emd_17191_half_map_1.map | ||||||||||||
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Annotation | Half-map2 resulting from gold standard refinement in RELION. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half-map1 resulting from gold standard refinement in RELION.
File | emd_17191_half_map_2.map | ||||||||||||
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Annotation | Half-map1 resulting from gold standard refinement in RELION. | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Human telomerase H/ACA RNP lobe
Entire | Name: Human telomerase H/ACA RNP lobe |
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Components |
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-Supramolecule #1: Human telomerase H/ACA RNP lobe
Supramolecule | Name: Human telomerase H/ACA RNP lobe / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all Details: The hTR H/ACA motif, which adopts a double-hairpin structure hinged by the H-box and flanked by the ACA box, scaffolds the assembly of two copies each of dyskerin, NHP2, NOP10 and GAR1, one ...Details: The hTR H/ACA motif, which adopts a double-hairpin structure hinged by the H-box and flanked by the ACA box, scaffolds the assembly of two copies each of dyskerin, NHP2, NOP10 and GAR1, one on each hairpin. TCAB1 binds the CAB box. |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 415 KDa |
-Supramolecule #2: Telomerase H/ACA RNP lobe
Supramolecule | Name: Telomerase H/ACA RNP lobe / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #2-#6 |
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Source (natural) | Organism: ![]() |
-Supramolecule #3: Human telomerase RNA
Supramolecule | Name: Human telomerase RNA / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Human telomerase RNA
Macromolecule | Name: Human telomerase RNA / 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: H/ACA ribonucleoprotein complex subunit DKC1
Macromolecule | Name: H/ACA ribonucleoprotein complex subunit DKC1 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 57.779211 KDa |
Sequence | String: MADAEVIILP KKHKKKKERK SLPEEDVAEI QHAEEFLIKP ESKVAKLDTS QWPLLLKNFD KLNVRTTHYT PLACGSNPLK REIGDYIRT GFINLDKPSN PSSHEVVAWI RRILRVEKTG HSGTLDPKVT GCLIVCIERA TRLVKSQQSA GKEYVGIVRL H NAIEGGTQ ...String: MADAEVIILP KKHKKKKERK SLPEEDVAEI QHAEEFLIKP ESKVAKLDTS QWPLLLKNFD KLNVRTTHYT PLACGSNPLK REIGDYIRT GFINLDKPSN PSSHEVVAWI RRILRVEKTG HSGTLDPKVT GCLIVCIERA TRLVKSQQSA GKEYVGIVRL H NAIEGGTQ LSRALETLTG ALFQRPPLIA AVKRQLRVRT IYESKMIEYD PERRLGIFWV SCEAGTYIRT LCVHLGLLLG VG GQMQELR RVRSGVMSEK DHMVTMHDVL DAQWLYDNHK DESYLRRVVY PLEKLLTSHK RLVMKDSAVN AICYGAKIML PGV LRYEDG IEVNQEIVVI TTKGEAICMA IALMTTAVIS TCDHGIVAKI KRVIMERDTY PRKWGLGPKA SQKKLMIKQG LLDK HGKPT DSTPATWKQE YVDYSESAKK EVVAEVVKAP QVVAEAAKTA KRKRESESES DETPPAAPQL IKKEKKKSKK DKKAK AGLE SGAEPGDGDS DTTKKKKKKK KAKEVELVSE UniProtKB: H/ACA ribonucleoprotein complex subunit DKC1 |
-Macromolecule #3: H/ACA ribonucleoprotein complex subunit 1
Macromolecule | Name: H/ACA ribonucleoprotein complex subunit 1 / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 22.387963 KDa |
Sequence | String: MSFRGGGRGG FNRGGGGGGF NRGGSSNHFR GGGGGGGGGN FRGGGRGGFG RGGGRGGFNK GQDQGPPERV VLLGEFLHPC EDDIVCKCT TDENKVPYFN APVYLENKEQ IGKVDEIFGQ LRDFYFSVKL SENMKASSFK KLQKFYIDPY KLLPLQRFLP R PPGEKGPP ...String: MSFRGGGRGG FNRGGGGGGF NRGGSSNHFR GGGGGGGGGN FRGGGRGGFG RGGGRGGFNK GQDQGPPERV VLLGEFLHPC EDDIVCKCT TDENKVPYFN APVYLENKEQ IGKVDEIFGQ LRDFYFSVKL SENMKASSFK KLQKFYIDPY KLLPLQRFLP R PPGEKGPP RGGGRGGRGG GRGGGGRGGG RGGGFRGGRG GGGGGFRGGR GGGFRGRGH UniProtKB: H/ACA ribonucleoprotein complex subunit 1 |
-Macromolecule #4: H/ACA ribonucleoprotein complex subunit 2
Macromolecule | Name: H/ACA ribonucleoprotein complex subunit 2 / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 17.22607 KDa |
Sequence | String: MTKIKADPDG PEAQAEACSG ERTYQELLVN QNPIAQPLAS RRLTRKLYKC IKKAVKQKQI RRGVKEVQKF VNKGEKGIMV LAGDTLPIE VYCHLPVMCE DRNLPYVYIP SKTDLGAAAG SKRPTCVIMV KPHEEYQEAY DECLEEVQSL PLPL UniProtKB: H/ACA ribonucleoprotein complex subunit 2 |
-Macromolecule #5: H/ACA ribonucleoprotein complex subunit 3
Macromolecule | Name: H/ACA ribonucleoprotein complex subunit 3 / type: protein_or_peptide / ID: 5 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 7.719989 KDa |
Sequence | String: MFLQYYLNEQ GDRVYTLKKF DPMGQQTCSA HPARFSPDDK YSRHRITIKK RFKVLMTQQP RPVL UniProtKB: H/ACA ribonucleoprotein complex subunit 3 |
-Macromolecule #6: Telomerase Cajal body protein 1
Macromolecule | Name: Telomerase Cajal body protein 1 / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 59.35707 KDa |
Sequence | String: MKTLETQPLA PDCCPSDQDP APAHPSPHAS PMNKNADSEL MPPPPERGDP PRLSPDPVAG SAVSQELREG DPVSLSTPLE TEFGSPSEL SPRIEEQELS ENTSLPAEEA NGSLSEEEAN GPELGSGKAM EDTSGEPAAE DEGDTAWNYS FSQLPRFLSG S WSEFSTQP ...String: MKTLETQPLA PDCCPSDQDP APAHPSPHAS PMNKNADSEL MPPPPERGDP PRLSPDPVAG SAVSQELREG DPVSLSTPLE TEFGSPSEL SPRIEEQELS ENTSLPAEEA NGSLSEEEAN GPELGSGKAM EDTSGEPAAE DEGDTAWNYS FSQLPRFLSG S WSEFSTQP ENFLKGCKWA PDGSCILTNS ADNILRIYNL PPELYHEGEQ VEYAEMVPVL RMVEGDTIYD YCWYSLMSSA QP DTSYVAS SSRENPIHIW DAFTGELRAS FRAYNHLDEL TAAHSLCFSP DGSQLFCGFN RTVRVFSTAR PGRDCEVRAT FAK KQGQSG IISCIAFSPA QPLYACGSYG RSLGLYAWDD GSPLALLGGH QGGITHLCFH PDGNRFFSGA RKDAELLCWD LRQS GYPLW SLGREVTTNQ RIYFDLDPTG QFLVSGSTSG AVSVWDTDGP GNDGKPEPVL SFLPQKDCTN GVSLHPSLPL LATAS GQRV FPEPTESGDE GEELGLPLLS TRHVHLECRL QLWWCGGAPD SSIPDDHQGE KGQGGTEGGV GELI UniProtKB: Telomerase Cajal body protein 1 |
-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 Component:
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Grid | Model: C-flat / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 5 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 12 sec. / Pretreatment - Atmosphere: AIR | |||||||||||||||||||||
Vitrification | Cryogen name: ETHANE / 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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Temperature | Min: 78.0 K |
Specialist optics | Energy filter - Name: GIF Quantum LS / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Digitization - Dimensions - Width: 5760 pixel / Digitization - Dimensions - Height: 4092 pixel / Number grids imaged: 2 / Number real images: 41053 / Average exposure time: 3.0 sec. / Average electron dose: 48.0 e/Å2 Details: Images were collected in movie-mode and fractionated into 48 movie frames |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 50.0 µm / Calibrated magnification: 45872 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 81000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |