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Yorodumi- PDB-7uck: 80S translation initiation complex with ac4c(-1) mRNA and Harring... -
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Open data
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Basic information
| Entry | Database: PDB / ID: 7uck | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Title | 80S translation initiation complex with ac4c(-1) mRNA and Harringtonine | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Keywords | RIBOSOME/INHIBITOR / Mammalian / 80S / initiation / complex / mRNA modification / mRNA acetylation / Harringtonine / RIBOSOME-INHIBITOR complex | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Function / homology | Function and homology informationregulation of translation involved in cellular response to UV / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / protein-DNA complex disassembly / positive regulation of DNA damage response, signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / positive regulation of signal transduction by p53 class mediator / phagocytic cup / negative regulation of ubiquitin-dependent protein catabolic process / translation regulator activity / ribosomal small subunit export from nucleus ...regulation of translation involved in cellular response to UV / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / protein-DNA complex disassembly / positive regulation of DNA damage response, signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / positive regulation of signal transduction by p53 class mediator / phagocytic cup / negative regulation of ubiquitin-dependent protein catabolic process / translation regulator activity / ribosomal small subunit export from nucleus / rough endoplasmic reticulum / positive regulation of apoptotic signaling pathway / MDM2/MDM4 family protein binding / DNA-(apurinic or apyrimidinic site) lyase / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / ribosomal large subunit biogenesis / DNA damage response, signal transduction by p53 class mediator / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of SSU-rRNA / positive regulation of translation / small-subunit processome / cellular response to gamma radiation / spindle / mRNA 5'-UTR binding / transcription coactivator binding / rRNA processing / cytosolic ribosome / glucose homeostasis / ribosomal small subunit assembly / ribosome binding / ribosomal small subunit biogenesis / small ribosomal subunit rRNA binding / 5S rRNA binding / ribosomal large subunit assembly / small ribosomal subunit / cytosolic small ribosomal subunit / large ribosomal subunit rRNA binding / cytosolic large ribosomal subunit / perikaryon / cytoplasmic translation / postsynaptic density / protein stabilization / rRNA binding / mitochondrial inner membrane / structural constituent of ribosome / ribosome / translation / mRNA binding / ubiquitin protein ligase binding / positive regulation of cell population proliferation / nucleolus / dendrite / synapse / negative regulation of transcription by RNA polymerase II / perinuclear region of cytoplasm / endoplasmic reticulum / RNA binding / zinc ion binding / nucleoplasm / membrane / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Biological species | ![]() | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Authors | Yang, R. / Arango, D. / Sturgill, D. / Oberdoerffer, S. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Funding support | United States, 1items
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Citation | Journal: Mol Cell / Year: 2022Title: Direct epitranscriptomic regulation of mammalian translation initiation through N4-acetylcytidine. Authors: Daniel Arango / David Sturgill / Renbin Yang / Tapan Kanai / Paulina Bauer / Jyoti Roy / Ziqiu Wang / Masaki Hosogane / Sarah Schiffers / Shalini Oberdoerffer / ![]() Abstract: mRNA function is influenced by modifications that modulate canonical nucleobase behavior. We show that a single modification mediates distinct impacts on mRNA translation in a position-dependent ...mRNA function is influenced by modifications that modulate canonical nucleobase behavior. We show that a single modification mediates distinct impacts on mRNA translation in a position-dependent manner. Although cytidine acetylation (ac4C) within protein-coding sequences stimulates translation, ac4C within 5' UTRs impacts protein synthesis at the level of initiation. 5' UTR acetylation promotes initiation at upstream sequences, competitively inhibiting annotated start codons. Acetylation further directly impedes initiation at optimal AUG contexts: ac4C within AUG-flanking Kozak sequences reduced initiation in base-resolved transcriptome-wide HeLa results and in vitro utilizing substrates with site-specific ac4C incorporation. Cryo-EM of mammalian 80S initiation complexes revealed that ac4C in the -1 position adjacent to an AUG start codon disrupts an interaction between C and hypermodified t6A at nucleotide 37 of the initiator tRNA. These findings demonstrate the impact of RNA modifications on nucleobase function at a molecular level and introduce mRNA acetylation as a factor regulating translation in a location-specific manner. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 7uck.cif.gz | 6.4 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb7uck.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 7uck.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/uc/7uck ftp://data.pdbj.org/pub/pdb/validation_reports/uc/7uck | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 26445MC ![]() 7ucjC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
-RNA chain , 6 types, 6 molecules 215789
| #1: RNA chain | Mass: 24721.828 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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| #2: RNA chain | Mass: 1957.250 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #3: RNA chain | Mass: 1150751.750 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #4: RNA chain | Mass: 38691.914 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #5: RNA chain | Mass: 49540.168 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #6: RNA chain | Mass: 548640.125 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
+60S ribosomal protein ... , 38 types, 38 molecules ABCEFGHJLMNOPQRSTUVXYZabcdefgh...
-Protein , 5 types, 5 molecules DAAVVAaGg
| #10: Protein | Mass: 33935.234 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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| #49: Protein | Mass: 24361.861 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #69: Protein | Mass: 9124.389 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #74: Protein | Mass: 11645.794 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #79: Protein | Mass: 34669.113 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Ribosomal protein ... , 3 types, 3 molecules IWFF
| #15: Protein | Mass: 24511.861 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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| #28: Protein | Mass: 14131.536 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
| #54: Protein | Mass: 21525.941 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
-Protein/peptide , 1 types, 1 molecules n
| #45: Protein/peptide | Mass: 3473.451 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() |
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+40S ribosomal protein ... , 26 types, 26 molecules BBCCDDEEGGHHIIJJKKLLNNOOPPQQRRSSTTUUWWXXYYZZBbCcDdEe
-Non-polymers , 3 types, 305 molecules 




| #80: Chemical | ChemComp-MG / #81: Chemical | ChemComp-MQ6 / | #82: Chemical | ChemComp-ZN / |
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-Details
| Has ligand of interest | Y |
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| Has protein modification | Y |
-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: 80S translation initiation complex with ac4C(-1) mRNA and Harringtonine Type: RIBOSOME / Entity ID: #1-#79 / Source: NATURAL |
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| Source (natural) | Organism: ![]() |
| Buffer solution | pH: 7.5 |
| 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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm |
| Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 107057 / Symmetry type: POINT | ||||||||||||||||||||||||
| Atomic model building | Space: REAL | ||||||||||||||||||||||||
| Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
| Displacement parameters | Biso mean: 81.66 Å2 | ||||||||||||||||||||||||
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