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- EMDB-17701: Structure of human 48S translation initiation complex with initia... -
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Open data
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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 / negative regulation of peptidyl-serine phosphorylation / 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 / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / translation at postsynapse / TNFR1-mediated ceramide production / negative regulation of DNA repair / negative regulation of RNA splicing / metal-dependent deubiquitinase activity / mammalian oogenesis stage / regulation of translational initiation / supercoiled DNA binding / activation-induced cell death of T cells / neural crest cell differentiation / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / NF-kappaB complex / oxidized purine DNA binding / cysteine-type endopeptidase activator activity involved in apoptotic process / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / translation at presynapse / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / negative regulation of phagocytosis / erythrocyte homeostasis / rRNA modification in the nucleus and cytosol / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / pigmentation / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / Translation initiation complex formation / positive regulation of mitochondrial depolarization / positive regulation of T cell receptor signaling pathway / positive regulation of activated T cell proliferation / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / monocyte chemotaxis / negative regulation of translational frameshifting / Protein hydroxylation / BH3 domain binding / TOR signaling / SARS-CoV-1 modulates host translation machinery / regulation of cell division / mTORC1-mediated signalling / T cell proliferation involved in immune response / Peptide chain elongation / iron-sulfur cluster binding / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / 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) / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / negative regulation of ubiquitin-dependent protein catabolic process / Viral mRNA Translation / negative regulation of respiratory burst involved in inflammatory response / phagocytic cup / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / erythrocyte development / Major pathway of rRNA processing in the nucleolus and cytosol / regulation of translational fidelity / 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) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Protein methylation / spindle assembly / Nuclear events stimulated by ALK signaling in cancer 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. | |||||||||
History |
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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 |
-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
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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 |