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- PDB-9q18: Class II ("T0D0") of Human telomerase catalytic core with shelter... -

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Basic information

Entry
Database: PDB / ID: 9q18
TitleClass II ("T0D0") of Human telomerase catalytic core with shelterin protein TPP1, BIBR1532, dGpNHpp and DNA primer ending in TTAG
Components
  • Adrenocortical dysplasia protein homolog
  • Histone H2A.J
  • Histone H2B type 1-C/E/F/G/I
  • Telomerase RNA
  • Telomerase reverse transcriptase
  • Telomeric repeat substrate
KeywordsRNA BINDING PROTEIN/RNA/DNA / DNA polymerase / Reverse Transcriptase / Ribonucleoprotein / RNA BINDING PROTEIN / RNA BINDING PROTEIN-RNA-DNA complex
Function / homology
Function and homology information


Regulation of PD-L1(CD274) transcription / telomere assembly / positive regulation of hair cycle / template-free RNA nucleotidyltransferase activity / positive regulation of transdifferentiation / TERT-RMRP complex / DNA strand elongation / RNA-directed RNA polymerase complex / segmentation / siRNA transcription ...Regulation of PD-L1(CD274) transcription / telomere assembly / positive regulation of hair cycle / template-free RNA nucleotidyltransferase activity / positive regulation of transdifferentiation / TERT-RMRP complex / DNA strand elongation / RNA-directed RNA polymerase complex / segmentation / siRNA transcription / positive regulation of protein localization to nucleolus / urogenital system development / telomerase catalytic core complex / protection from non-homologous end joining at telomere / RNA-templated DNA biosynthetic process / establishment of protein localization to telomere / regulation of establishment of protein localization to telomere / telomerase activity / telomerase inhibitor activity / shelterin complex / Telomere C-strand synthesis initiation / Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence / Telomere C-strand (Lagging Strand) Synthesis / siRNA processing / nuclear telomere cap complex / telomere capping / telomere maintenance via recombination / Polymerase switching on the C-strand of the telomere / telomerase holoenzyme complex / positive regulation of vascular associated smooth muscle cell migration / telomerase RNA binding / Processive synthesis on the C-strand of the telomere / embryonic limb morphogenesis / Removal of the Flap Intermediate from the C-strand / protein localization to chromosome, telomeric region / DNA biosynthetic process / RNA-templated transcription / positive regulation of stem cell proliferation / telomeric repeat DNA binding / negative regulation of telomere maintenance via telomerase / positive regulation of telomere maintenance / negative regulation of cellular senescence / mitochondrial nucleoid / replicative senescence / Telomere Extension By Telomerase / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / response to cadmium ion / negative regulation of endothelial cell apoptotic process / telomere maintenance via telomerase / positive regulation of G1/S transition of mitotic cell cycle / positive regulation of Wnt signaling pathway / positive regulation of vascular associated smooth muscle cell proliferation / Replacement of protamines by nucleosomes in the male pronucleus / DNA polymerase binding / Packaging Of Telomere Ends / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / Deposition of new CENPA-containing nucleosomes at the centromere / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / telomere maintenance / RNA Polymerase I Promoter Opening / Inhibition of DNA recombination at telomere / Assembly of the ORC complex at the origin of replication / Meiotic synapsis / Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex / DNA methylation / Condensation of Prophase Chromosomes / positive regulation of D-glucose import across plasma membrane / Chromatin modifications during the maternal to zygotic transition (MZT) / SIRT1 negatively regulates rRNA expression / HCMV Late Events / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / PRC2 methylates histones and DNA / Regulation of endogenous retroelements by KRAB-ZFP proteins / innate immune response in mucosa / Defective pyroptosis / skeletal system development / HDACs deacetylate histones / mitochondrion organization / Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) / RNA Polymerase I Promoter Escape / Nonhomologous End-Joining (NHEJ) / regulation of protein stability / Transcriptional regulation by small RNAs / Formation of the beta-catenin:TCF transactivating complex / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / intracellular protein transport / PML body / NoRC negatively regulates rRNA expression / Negative Regulation of CDH1 Gene Transcription / G2/M DNA damage checkpoint / RNA-directed DNA polymerase / positive regulation of miRNA transcription / B-WICH complex positively regulates rRNA expression / DNA Damage/Telomere Stress Induced Senescence / Meiotic recombination / Pre-NOTCH Transcription and Translation / RNA-directed DNA polymerase activity
Similarity search - Function
Adrenocortical dysplasia protein / : / Telomerase reverse transcriptase, C-terminal extension / Shelterin complex subunit TPP1/Est3 / Shelterin complex subunit, TPP1/ACD / Telomerase ribonucleoprotein complex - RNA binding domain / Telomerase reverse transcriptase / Telomerase ribonucleoprotein complex - RNA-binding domain / Telomerase ribonucleoprotein complex - RNA binding domain / : ...Adrenocortical dysplasia protein / : / Telomerase reverse transcriptase, C-terminal extension / Shelterin complex subunit TPP1/Est3 / Shelterin complex subunit, TPP1/ACD / Telomerase ribonucleoprotein complex - RNA binding domain / Telomerase reverse transcriptase / Telomerase ribonucleoprotein complex - RNA-binding domain / Telomerase ribonucleoprotein complex - RNA binding domain / : / Histone H2A conserved site / Histone H2A signature. / Histone H2B signature. / Histone H2B / Histone H2B / Histone H2A, C-terminal domain / C-terminus of histone H2A / Histone 2A / Histone H2A / Reverse transcriptase domain / Reverse transcriptase (RT) catalytic domain profile. / Histone H2A/H2B/H3 / Core histone H2A/H2B/H3/H4 domain / Histone-fold / DNA/RNA polymerase superfamily
Similarity search - Domain/homology
Chem-55C / : / DNA / DNA (> 10) / RNA / RNA (> 10) / RNA (> 100) / Telomerase reverse transcriptase / Histone H2B type 1-C/E/F/G/I / Adrenocortical dysplasia protein homolog / Histone H2A.J
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsWang, Y. / Liu, B. / He, Y. / Feigon, J.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R35GM131901 United States
National Science Foundation (NSF, United States)MCB2016540 United States
CitationJournal: To Be Published
Title: Structures of telomerase with BIBR1532 reveal novel mechanism of inhibition
Authors: Wang, Y. / Liu, B. / He, Y. / Feigon, J.
History
DepositionAug 13, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 17, 2026Provider: repository / Type: Initial release
Revision 1.0Jun 17, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Jun 17, 2026Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Jun 17, 2026Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jun 17, 2026Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jun 17, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Jun 17, 2026Data content type: Mask / Part number: 1 / Data content type: Mask / Provider: repository / Type: Initial release
Revision 1.0Jun 17, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Telomerase reverse transcriptase
B: Telomerase RNA
C: Adrenocortical dysplasia protein homolog
D: Telomeric repeat substrate
F: Histone H2A.J
G: Histone H2B type 1-C/E/F/G/I
hetero molecules


Theoretical massNumber of molelcules
Total (without water)327,8617
Polymers327,5296
Non-polymers3311
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Protein , 4 types, 4 molecules ACFG

#1: Protein Telomerase reverse transcriptase / HEST2 / Telomerase catalytic subunit / Telomerase-associated protein 2 / TP2


Mass: 130711.492 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TERT, EST2, TCS1, TRT / Production host: Homo sapiens (human) / References: UniProt: O14746, RNA-directed DNA polymerase
#3: Protein Adrenocortical dysplasia protein homolog / POT1 and TIN2-interacting protein


Mass: 17672.637 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ACD, PIP1, PTOP, TINT1, TPP1 / Production host: Escherichia coli (E. coli) / References: UniProt: Q96AP0
#5: Protein Histone H2A.J / H2a/j


Mass: 14047.451 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: Q9BTM1
#6: Protein Histone H2B type 1-C/E/F/G/I / Histone H2B.1 A / Histone H2B.a / H2B/a / Histone H2B.g / H2B/g / Histone H2B.h / H2B/h / Histone ...Histone H2B.1 A / Histone H2B.a / H2B/a / Histone H2B.g / H2B/g / Histone H2B.h / H2B/h / Histone H2B.k / H2B/k / Histone H2B.l / H2B/l


Mass: 13937.213 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P62807

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RNA chain / DNA chain / Non-polymers , 3 types, 3 molecules BD

#2: RNA chain Telomerase RNA


Mass: 145477.797 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) / References: GenBank: 1932797
#4: DNA chain Telomeric repeat substrate


Mass: 5682.672 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human)
#7: Chemical ChemComp-55C / 2-{[(2E)-3-(naphthalen-2-yl)but-2-enoyl]amino}benzoic acid / BIBR 1532


Mass: 331.365 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H17NO3 / Feature type: SUBJECT OF INVESTIGATION

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Details

Has ligand of interestY
Has protein modificationN

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

Component
IDNameTypeEntity IDParent-IDSource
1Class II ("T0D0") of Human telomerase catalytic core with shelterin protein TPP1, BIBR1532, dGpNHpp and DNA primer ending in TTAGCOMPLEX#1-#60MULTIPLE SOURCES
2Telomerase RNACOMPLEX#21RECOMBINANT
3Telomerase reverse transcriptaseCOMPLEX#11RECOMBINANT
4Adrenocortical dysplasia protein homologCOMPLEX#31RECOMBINANT
5DNA primerCOMPLEX#41SYNTHETIC
6Histones H2A and H2BCOMPLEX#5-#61NATURAL
Molecular weightExperimental value: NO
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
22Homo sapiens (human)9606
33Homo sapiens (human)9606
44Homo sapiens (human)9606
55Homo sapiens (human)9606
66Homo sapiens (human)9606
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-ID
22Homo sapiens (human)9606
33Homo sapiens (human)9606
44Escherichia coli (E. coli)562
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE-PROPANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 500 nm
Image recordingElectron dose: 45 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM software
IDNameCategory
1cryoSPARCparticle selection
2Topazparticle selection
14cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.3 Å / Resolution method: FSC 0.33 CUT-OFF / Num. of particles: 394237 / Symmetry type: POINT
RefinementHighest resolution: 3.3 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00415481
ELECTRON MICROSCOPYf_angle_d0.65322000
ELECTRON MICROSCOPYf_dihedral_angle_d18.9587117
ELECTRON MICROSCOPYf_chiral_restr0.0372647
ELECTRON MICROSCOPYf_plane_restr0.0062023

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