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- EMDB-17701: Structure of human 48S translation initiation complex with initia... -
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Basic information
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Title | Structure of human 48S translation initiation complex with initiator tRNA, eIF1A and eIF3 (off-pathway) | |||||||||
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![]() | RIBOSOME / TRANSLATION / initiation / 48S / eIF / human / eukaryotic / factor / codon / scanning / closed | |||||||||
Function / homology | ![]() positive regulation of mRNA binding / viral translational termination-reinitiation / eukaryotic translation initiation factor 3 complex, eIF3e / cap-dependent translational initiation / eukaryotic translation initiation factor 3 complex, eIF3m / IRES-dependent viral translational initiation / translation reinitiation / eukaryotic translation initiation factor 3 complex / formation of cytoplasmic translation initiation complex / cytoplasmic translational initiation ...positive regulation of mRNA binding / viral translational termination-reinitiation / eukaryotic translation initiation factor 3 complex, eIF3e / cap-dependent translational initiation / eukaryotic translation initiation factor 3 complex, eIF3m / IRES-dependent viral translational initiation / translation reinitiation / eukaryotic translation initiation factor 3 complex / formation of cytoplasmic translation initiation complex / cytoplasmic translational initiation / multi-eIF complex / translation factor activity, RNA binding / eukaryotic 43S preinitiation complex / mRNA cap binding / eukaryotic 48S preinitiation complex / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / positive regulation of respiratory burst involved in inflammatory response / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / protein tyrosine kinase inhibitor activity / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / nucleolus organization / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / negative regulation of DNA repair / negative regulation of RNA splicing / metal-dependent deubiquitinase activity / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / supercoiled DNA binding / neural crest cell differentiation / NF-kappaB complex / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / positive regulation of ubiquitin-protein transferase activity / cysteine-type endopeptidase activator activity involved in apoptotic process / regulation of translational initiation / oxidized purine DNA binding / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / ubiquitin-like protein conjugating enzyme binding / negative regulation of bicellular tight junction assembly / regulation of establishment of cell polarity / negative regulation of phagocytosis / rRNA modification in the nucleus and cytosol / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / negative regulation of ubiquitin protein ligase activity / protein kinase A binding / ion channel inhibitor activity / pigmentation / Ribosomal scanning and start codon recognition / Translation initiation complex formation / positive regulation of mitochondrial depolarization / positive regulation of T cell receptor signaling pathway / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / monocyte chemotaxis / positive regulation of activated T cell proliferation / negative regulation of translational frameshifting / Protein hydroxylation / TOR signaling / BH3 domain binding / regulation of cell division / SARS-CoV-1 modulates host translation machinery / mTORC1-mediated signalling / cellular response to ethanol / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / iron-sulfur cluster binding / Peptide chain elongation / Selenocysteine synthesis / Formation of a pool of free 40S subunits / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Eukaryotic Translation Termination / ubiquitin ligase inhibitor activity / Response of EIF2AK4 (GCN2) to amino acid deficiency / negative regulation of ubiquitin-dependent protein catabolic process / positive regulation of signal transduction by p53 class mediator / SRP-dependent cotranslational protein targeting to membrane / protein serine/threonine kinase inhibitor activity / Viral mRNA Translation / negative regulation of respiratory burst involved in inflammatory response / Maturation of protein E / Maturation of protein E / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / Prevention of phagosomal-lysosomal fusion / L13a-mediated translational silencing of Ceruloplasmin expression / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||
![]() | Petrychenko V / Yi S-H / Liedtke D / Peng BZ / Rodnina MV / Fischer N | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis for translational control by the human 48S initiation complex. Authors: Valentyn Petrychenko / Sung-Hui Yi / David Liedtke / Bee-Zen Peng / Marina V Rodnina / Niels Fischer / ![]() Abstract: The selection of an open reading frame (ORF) for translation of eukaryotic mRNA relies on remodeling of the scanning 48S initiation complex into an elongation-ready 80S ribosome. Using cryo-electron ...The selection of an open reading frame (ORF) for translation of eukaryotic mRNA relies on remodeling of the scanning 48S initiation complex into an elongation-ready 80S ribosome. Using cryo-electron microscopy, we visualize the key commitment steps orchestrating 48S remodeling in humans. The mRNA Kozak sequence facilitates mRNA scanning in the 48S open state and stabilizes the 48S closed state by organizing the contacts of eukaryotic initiation factors (eIFs) and ribosomal proteins and by reconfiguring mRNA structure. GTPase-triggered large-scale fluctuations of 48S-bound eIF2 facilitate eIF5B recruitment, transfer of initiator tRNA from eIF2 to eIF5B and the release of eIF5 and eIF2. The 48S-bound multisubunit eIF3 complex controls ribosomal subunit joining by coupling eIF exchange to gradual displacement of the eIF3c N-terminal domain from the intersubunit interface. These findings reveal the structural mechanism of ORF selection in human cells and explain how eIF3 could function in the context of the 80S ribosome. | |||||||||
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 140.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 72.6 KB 72.6 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 12.7 KB | Display | ![]() |
Images | ![]() | 150.7 KB | ||
Masks | ![]() | 178 MB | ![]() | |
Filedesc metadata | ![]() | 17.6 KB | ||
Others | ![]() ![]() | 140.6 MB 140.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 987 KB | Display | ![]() |
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Full document | ![]() | 986.6 KB | Display | |
Data in XML | ![]() | 20.4 KB | Display | |
Data in CIF | ![]() | 27 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8pj6MC ![]() 8pj1C ![]() 8pj2C ![]() 8pj3C ![]() 8pj4C ![]() 8pj5C ![]() 8rg0C 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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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.16 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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Density Histograms |
-Half map: #2
File | emd_17701_half_map_1.map | ||||||||||||
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Density Histograms |
-Half map: #1
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Density Histograms |
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Sample components
+Entire : Human 48S initiation complex 40S-eIF1A-eIF3-tRNA-Met-mRNA
+Supramolecule #1: Human 48S initiation complex 40S-eIF1A-eIF3-tRNA-Met-mRNA
+Macromolecule #1: Eukaryotic translation initiation factor 3 subunit B
+Macromolecule #2: Eukaryotic translation initiation factor 3 subunit I
+Macromolecule #3: Eukaryotic translation initiation factor 3 subunit K
+Macromolecule #4: Eukaryotic translation initiation factor 3 subunit F
+Macromolecule #5: Eukaryotic translation initiation factor 3 subunit L
+Macromolecule #6: Eukaryotic translation initiation factor 3 subunit M
+Macromolecule #8: Eukaryotic translation initiation factor 3 subunit H
+Macromolecule #9: 60S ribosomal protein L41
+Macromolecule #11: 40S ribosomal protein S11
+Macromolecule #12: 40S ribosomal protein S4, X isoform
+Macromolecule #13: 40S ribosomal protein S9
+Macromolecule #14: 40S ribosomal protein S23
+Macromolecule #15: 40S ribosomal protein S30
+Macromolecule #16: 40S ribosomal protein S7
+Macromolecule #17: 40S ribosomal protein S27
+Macromolecule #18: 40S ribosomal protein S13
+Macromolecule #19: 40S ribosomal protein S15a
+Macromolecule #20: 40S ribosomal protein S21
+Macromolecule #21: 40S ribosomal protein S2
+Macromolecule #22: 40S ribosomal protein S17
+Macromolecule #23: 40S ribosomal protein SA
+Macromolecule #24: 40S ribosomal protein S3a
+Macromolecule #25: 40S ribosomal protein S14
+Macromolecule #26: 40S ribosomal protein S26
+Macromolecule #27: 40S ribosomal protein S8
+Macromolecule #28: 40S ribosomal protein S6
+Macromolecule #29: 40S ribosomal protein S24
+Macromolecule #30: 40S ribosomal protein S5
+Macromolecule #31: 40S ribosomal protein S16
+Macromolecule #32: 40S ribosomal protein S3
+Macromolecule #33: 40S ribosomal protein S10
+Macromolecule #34: 40S ribosomal protein S15
+Macromolecule #35: Receptor of activated protein C kinase 1
+Macromolecule #36: 40S ribosomal protein S19
+Macromolecule #37: 40S ribosomal protein S25
+Macromolecule #38: 40S ribosomal protein S18
+Macromolecule #39: 40S ribosomal protein S20
+Macromolecule #40: 40S ribosomal protein S29
+Macromolecule #41: Ubiquitin
+Macromolecule #42: 40S ribosomal protein S12
+Macromolecule #43: 40S ribosomal protein S28
+Macromolecule #44: Eukaryotic translation initiation factor 3 subunit G
+Macromolecule #45: Eukaryotic translation initiation factor 1A, X-chromosomal
+Macromolecule #46: Eukaryotic translation initiation factor 3 subunit A
+Macromolecule #47: Eukaryotic translation initiation factor 3 subunit E
+Macromolecule #49: Eukaryotic translation initiation factor 3 subunit D
+Macromolecule #50: Eukaryotic translation initiation factor 3 subunit C
+Macromolecule #7: mRNA
+Macromolecule #10: 18S rRNA
+Macromolecule #48: Initiator Met-tRNA-i
+Macromolecule #51: MAGNESIUM ION
+Macromolecule #52: ZINC ION
-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: 7.5 Component:
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Vitrification | Cryogen name: ETHANE / Instrument: HOMEMADE PLUNGER / Details: Manual blotting & plunge-freezing. |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Spherical aberration corrector: Electron-optical aberrations were corrected using a CETCOR Cs-corrector (CEOS, Heidelberg) aligned with the CETCORPLUS 4.6.9 software package (CEOS, Heidelberg). |
Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Average exposure time: 1.5 sec. / Average electron dose: 45.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.2 µm / Nominal magnification: 59000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |