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Yorodumi- EMDB-26445: 80S translation initiation complex with ac4c(-1) mRNA and Harring... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-26445 | |||||||||
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Title | 80S translation initiation complex with ac4c(-1) mRNA and Harringtonine | |||||||||
Map data | Consensus map by combining local refined maps. | |||||||||
Sample |
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Function / homology | Function and homology information ribosomal subunit / regulation of G1 to G0 transition / exit from mitosis / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / regulation of translation involved in cellular response to UV / protein-DNA complex disassembly / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / optic nerve development / retinal ganglion cell axon guidance / mammalian oogenesis stage ...ribosomal subunit / regulation of G1 to G0 transition / exit from mitosis / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / regulation of translation involved in cellular response to UV / protein-DNA complex disassembly / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / optic nerve development / retinal ganglion cell axon guidance / mammalian oogenesis stage / G1 to G0 transition / activation-induced cell death of T cells / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / phagocytic cup / 90S preribosome / TOR signaling / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / T cell proliferation involved in immune response / erythrocyte development / cellular response to actinomycin D / negative regulation of ubiquitin-dependent protein catabolic process / ribosomal small subunit export from nucleus / translation regulator activity / rough endoplasmic reticulum / endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / gastrulation / MDM2/MDM4 family protein binding / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / cytosolic ribosome / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / rescue of stalled ribosome / ribosomal large subunit biogenesis / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of SSU-rRNA / positive regulation of translation / small-subunit processome / protein kinase C binding / positive regulation of apoptotic signaling pathway / positive regulation of protein-containing complex assembly / placenta development / cellular response to gamma radiation / mRNA 5'-UTR binding / transcription coactivator binding / spindle / cytoplasmic ribonucleoprotein granule / G1/S transition of mitotic cell cycle / rRNA processing / ribosomal small subunit biogenesis / antimicrobial humoral immune response mediated by antimicrobial peptide / rhythmic process / small ribosomal subunit rRNA binding / ribosome binding / glucose homeostasis / regulation of translation / ribosomal small subunit assembly / retina development in camera-type eye / small ribosomal subunit / 5S rRNA binding / large ribosomal subunit rRNA binding / T cell differentiation in thymus / cytosolic small ribosomal subunit / ribosomal large subunit assembly / cell body / cytoplasmic translation / perikaryon / cytosolic large ribosomal subunit / defense response to Gram-negative bacterium / killing of cells of another organism / tRNA binding / mitochondrial inner membrane / postsynaptic density / cell differentiation / protein stabilization / rRNA binding / ribosome / structural constituent of ribosome / positive regulation of apoptotic process / positive regulation of protein phosphorylation / ribonucleoprotein complex / translation / cell division / DNA repair / mRNA binding / dendrite / ubiquitin protein ligase binding / positive regulation of cell population proliferation / synapse / positive regulation of gene expression / negative regulation of apoptotic process / nucleolus / apoptotic process / protein kinase binding / perinuclear region of cytoplasm / negative regulation of transcription by RNA polymerase II / endoplasmic reticulum / DNA binding / RNA binding Similarity search - Function | |||||||||
Biological species | Oryctolagus cuniculus (rabbit) / rabbit (rabbit) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||
Authors | Yang R / Arango D / Sturgill D / Oberdoerffer S | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Mol Cell / Year: 2022 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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_26445.map.gz | 12.3 MB | EMDB map data format | |
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Header (meta data) | emd-26445-v30.xml emd-26445.xml | 91.7 KB 91.7 KB | Display Display | EMDB header |
Images | emd_26445.png | 68.8 KB | ||
Others | emd_26445_additional_1.map.gz emd_26445_additional_2.map.gz emd_26445_additional_3.map.gz | 22.9 MB 20.9 MB 5.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-26445 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26445 | HTTPS FTP |
-Validation report
Summary document | emd_26445_validation.pdf.gz | 355.3 KB | Display | EMDB validaton report |
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Full document | emd_26445_full_validation.pdf.gz | 354.8 KB | Display | |
Data in XML | emd_26445_validation.xml.gz | 7.6 KB | Display | |
Data in CIF | emd_26445_validation.cif.gz | 8.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26445 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26445 | HTTPS FTP |
-Related structure data
Related structure data | 7uckMC 7ucjC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_26445.map.gz / Format: CCP4 / Size: 421.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Consensus map by combining local refined maps. | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.358 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: Composite map from ribosome large submit (LSU).
File | emd_26445_additional_1.map | ||||||||||||
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Annotation | Composite map from ribosome large submit (LSU). | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Composite map from ribosome small submit (SSU).
File | emd_26445_additional_2.map | ||||||||||||
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Annotation | Composite map from ribosome small submit (SSU). | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Composite map on mRNA focus refinement.
File | emd_26445_additional_3.map | ||||||||||||
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Annotation | Composite map on mRNA focus refinement. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : 80S translation initiation complex with ac4C(-1) mRNA and Harring...
+Supramolecule #1: 80S translation initiation complex with ac4C(-1) mRNA and Harring...
+Macromolecule #1: P-site tRNA
+Macromolecule #2: mRNA
+Macromolecule #3: 28s rRNA
+Macromolecule #4: 5S rRNA
+Macromolecule #5: 5.8S rRNA
+Macromolecule #6: 18S rRNA
+Macromolecule #7: 60S ribosomal protein L8
+Macromolecule #8: 60S ribosomal protein L3
+Macromolecule #9: 60S ribosomal protein L4
+Macromolecule #10: Ribosomal_L18_c domain-containing protein
+Macromolecule #11: 60S ribosomal protein L6
+Macromolecule #12: 60S ribosomal protein L7
+Macromolecule #13: 60S ribosomal protein L7a
+Macromolecule #14: 60S ribosomal protein L9
+Macromolecule #15: Ribosomal protein L10
+Macromolecule #16: 60S ribosomal protein L11
+Macromolecule #17: 60S ribosomal protein L13
+Macromolecule #18: 60S ribosomal protein L14
+Macromolecule #19: 60S ribosomal protein L15
+Macromolecule #20: 60S ribosomal protein L13a
+Macromolecule #21: 60S ribosomal protein L17
+Macromolecule #22: 60S ribosomal protein L18
+Macromolecule #23: 60S ribosomal protein L19
+Macromolecule #24: 60S ribosomal protein L18a
+Macromolecule #25: 60S ribosomal protein L21
+Macromolecule #26: 60S ribosomal protein L22
+Macromolecule #27: 60S ribosomal protein L23
+Macromolecule #28: Ribosomal protein L24
+Macromolecule #29: 60S ribosomal protein L23a
+Macromolecule #30: 60S ribosomal protein L26
+Macromolecule #31: 60S ribosomal protein L27
+Macromolecule #32: 60S ribosomal protein L27a
+Macromolecule #33: 60S ribosomal protein L29
+Macromolecule #34: 60S ribosomal protein L30
+Macromolecule #35: 60S ribosomal protein L31
+Macromolecule #36: 60S ribosomal protein L32
+Macromolecule #37: 60S ribosomal protein L35a
+Macromolecule #38: 60S ribosomal protein L34
+Macromolecule #39: 60S ribosomal protein L35
+Macromolecule #40: 60S ribosomal protein L36
+Macromolecule #41: 60S ribosomal protein L37
+Macromolecule #42: 60S ribosomal protein L38
+Macromolecule #43: 60S ribosomal protein L39
+Macromolecule #44: 60S ribosomal protein L40
+Macromolecule #45: eL41
+Macromolecule #46: 60S ribosomal protein L36a
+Macromolecule #47: 60S ribosomal protein L37a
+Macromolecule #48: 60S ribosomal protein L28
+Macromolecule #49: 40S_SA_C domain-containing protein
+Macromolecule #50: 40S ribosomal protein S3a
+Macromolecule #51: 40S ribosomal protein S2
+Macromolecule #52: 40S ribosomal protein S3
+Macromolecule #53: 40S ribosomal protein S4
+Macromolecule #54: Ribosomal protein S5
+Macromolecule #55: 40S ribosomal protein S6
+Macromolecule #56: 40S ribosomal protein S7
+Macromolecule #57: 40S ribosomal protein S8
+Macromolecule #58: 40S ribosomal protein S9
+Macromolecule #59: 40S ribosomal protein S10
+Macromolecule #60: 40S ribosomal protein S11
+Macromolecule #61: 40S ribosomal protein S13
+Macromolecule #62: 40S ribosomal protein S14
+Macromolecule #63: 40S ribosomal protein S15
+Macromolecule #64: 40S ribosomal protein S16
+Macromolecule #65: 40S ribosomal protein S17
+Macromolecule #66: 40S ribosomal protein S18
+Macromolecule #67: 40S ribosomal protein S19
+Macromolecule #68: 40S ribosomal protein S20
+Macromolecule #69: eS21
+Macromolecule #70: 40S ribosomal protein S15a
+Macromolecule #71: 40S ribosomal protein S23
+Macromolecule #72: 40S ribosomal protein S24
+Macromolecule #73: 40S ribosomal protein S25
+Macromolecule #74: eS26
+Macromolecule #75: 40S ribosomal protein S27
+Macromolecule #76: 40S ribosomal protein S28
+Macromolecule #77: 40S ribosomal protein S29
+Macromolecule #78: 40S ribosomal protein S30
+Macromolecule #79: Receptor of activated protein C kinase 1
+Macromolecule #80: MAGNESIUM ION
+Macromolecule #81: Harringtonine
+Macromolecule #82: ZINC ION
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER / Details: By 3D volumes from negative staining dataset. |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 107057 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
-Atomic model buiding 1
Refinement | Space: REAL |
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Output model | PDB-7uck: |