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- 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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![]() | RIBOSOME/INHIBITOR / Mammalian / 80S / initiation / complex / mRNA modification / mRNA acetylation / Harringtonine / RIBOSOME-INHIBITOR complex | ||||||
Function / homology | ![]() ribosomal subunit / exit from mitosis / optic nerve development / retinal ganglion cell axon guidance / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / phagocytic cup / ribosomal small subunit export from nucleus / rough endoplasmic reticulum / translation regulator activity ...ribosomal subunit / exit from mitosis / optic nerve development / retinal ganglion cell axon guidance / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / phagocytic cup / ribosomal small subunit export from nucleus / rough endoplasmic reticulum / translation regulator activity / gastrulation / MDM2/MDM4 family protein binding / cytosolic ribosome / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / positive regulation of apoptotic signaling pathway / maturation of SSU-rRNA / small-subunit processome / spindle / mRNA 5'-UTR binding / antimicrobial humoral immune response mediated by antimicrobial peptide / rRNA processing / rhythmic process / regulation of translation / large ribosomal subunit / ribosome binding / ribosomal small subunit biogenesis / ribosomal small subunit assembly / retina development in camera-type eye / small ribosomal subunit / 5S rRNA binding / ribosomal large subunit assembly / cytosolic small ribosomal subunit / large ribosomal subunit rRNA binding / small ribosomal subunit rRNA binding / defense response to Gram-negative bacterium / killing of cells of another organism / perikaryon / cytosolic large ribosomal subunit / cytoplasmic translation / cell differentiation / tRNA binding / mitochondrial inner membrane / postsynaptic density / rRNA binding / ribosome / structural constituent of ribosome / translation / ribonucleoprotein complex / cell division / DNA repair / mRNA binding / apoptotic process / synapse / dendrite / negative regulation of apoptotic process / nucleolus / perinuclear region of cytoplasm / endoplasmic reticulum / DNA binding / RNA binding / zinc ion binding / nucleus / membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å | ||||||
![]() | Yang, R. / Arango, D. / Sturgill, D. / Oberdoerffer, S. | ||||||
Funding support | ![]()
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![]() | ![]() Title: 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. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 6.4 MB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | 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 ![]() |
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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: ![]() |
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 | ||||||||||||||||||||||||
Refine LS restraints |
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