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- EMDB-17297: Structure of a human 48S translation initiation complex with eIF4... -
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Basic information
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Title | Structure of a human 48S translation initiation complex with eIF4F and eIF4A | ||||||||||||
![]() | Human 48S complex | ||||||||||||
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![]() | translation / eIF4A / eIF4F / initiation / ribosome / mRNA | ||||||||||||
Function / homology | ![]() positive regulation of eukaryotic translation initiation factor 4F complex assembly / : / male germ cell proliferation / eukaryotic initiation factor eIF2 binding / positive regulation of mRNA binding / translation initiation ternary complex / regulation of translation in response to endoplasmic reticulum stress / glial limiting end-foot / positive regulation of translation in response to endoplasmic reticulum stress / HRI-mediated signaling ...positive regulation of eukaryotic translation initiation factor 4F complex assembly / : / male germ cell proliferation / eukaryotic initiation factor eIF2 binding / positive regulation of mRNA binding / translation initiation ternary complex / regulation of translation in response to endoplasmic reticulum stress / glial limiting end-foot / positive regulation of translation in response to endoplasmic reticulum stress / HRI-mediated signaling / response to kainic acid / macromolecule biosynthetic process / viral translational termination-reinitiation / Cellular response to mitochondrial stress / response to manganese-induced endoplasmic reticulum stress / positive regulation of type B pancreatic cell apoptotic process / eukaryotic translation initiation factor 3 complex, eIF3e / Response of EIF2AK1 (HRI) to heme deficiency / Recycling of eIF2:GDP / cap-dependent translational initiation / negative regulation of translational initiation in response to stress / PERK-mediated unfolded protein response / methionyl-initiator methionine tRNA binding / Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / eukaryotic translation initiation factor 3 complex, eIF3m / eukaryotic initiation factor 4E binding / PERK regulates gene expression / regulation of cellular response to stress / IRES-dependent viral translational initiation / translation reinitiation / eukaryotic translation initiation factor 2 complex / eukaryotic translation initiation factor 3 complex / nuclear stress granule / RNA cap binding / eukaryotic translation initiation factor 4F complex / formation of cytoplasmic translation initiation complex / cytoplasmic translational initiation / multi-eIF complex / Z-decay: degradation of maternal mRNAs by zygotically expressed factors / regulation of translational initiation in response to stress / translation factor activity, RNA binding / eukaryotic 43S preinitiation complex / mRNA cap binding / formation of translation preinitiation complex / Deadenylation of mRNA / miRNA-mediated gene silencing by inhibition of translation / negative regulation of peptidyl-threonine phosphorylation / eukaryotic 48S preinitiation complex / M-decay: degradation of maternal mRNAs by maternally stored factors / 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 / protein-synthesizing GTPase / negative regulation of DNA repair / negative regulation of RNA splicing / metal-dependent deubiquitinase activity / mammalian oogenesis stage / regulation of translational initiation / positive regulation of protein localization to cell periphery / 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 / GDP-dissociation inhibitor activity / 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 Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||||||||
![]() | Brito Querido J / Sokabe M / Diaz-Lopez I / Gordiyenko Y / Fraser CS / Ramakrishnan V | ||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: The structure of a human translation initiation complex reveals two independent roles for the helicase eIF4A. Authors: Jailson Brito Querido / Masaaki Sokabe / Irene Díaz-López / Yuliya Gordiyenko / Christopher S Fraser / V Ramakrishnan / ![]() ![]() Abstract: Eukaryotic translation initiation involves recruitment of the 43S pre-initiation complex to the 5' end of mRNA by the cap-binding complex eIF4F, forming the 48S translation initiation complex (48S), ...Eukaryotic translation initiation involves recruitment of the 43S pre-initiation complex to the 5' end of mRNA by the cap-binding complex eIF4F, forming the 48S translation initiation complex (48S), which then scans along the mRNA until the start codon is recognized. We have previously shown that eIF4F binds near the mRNA exit channel of the 43S, leaving open the question of how mRNA secondary structure is removed as it enters the mRNA channel on the other side of the 40S subunit. Here we report the structure of a human 48S that shows that, in addition to the eIF4A that is part of eIF4F, there is a second eIF4A helicase bound at the mRNA entry site, which could unwind RNA secondary structures as they enter the 48S. The structure also reveals conserved interactions between eIF4F and the 43S, probaby explaining how eIF4F can promote mRNA recruitment in all eukaryotes. | ||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 32.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 108.8 KB 108.8 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 14.2 KB | Display | ![]() |
Images | ![]() | 85.4 KB | ||
Masks | ![]() | 244.1 MB | ![]() | |
Filedesc metadata | ![]() | 20.8 KB | ||
Others | ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() | 190.3 MB 13 MB 209.8 MB 152.6 MB 144.3 MB 209.3 MB 139.3 MB 5.1 MB 3.4 MB 192.5 MB 8.6 MB 194.6 MB 193.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8oz0MC 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
File | ![]() | ||||||||||||||||||||||||||||||||||||
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Annotation | Human 48S complex | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
+Mask #1
+Additional map: Body1 - 3D multi-body refinement of 48S
+Additional map: eIF3 after focus 4F
+Additional map: PIC after focus EntrySite
+Additional map: Body2 - 3D multi-body refinement of 48S
+Additional map: Body3 - 3D multi-body refinement of 48S
+Additional map: PIC after focus EntrySite Resampled map
+Additional map: eIF4F-eIF3 after focus EntrySite Resampled map
+Additional map: eIF3 after focus 4F Resampled map
+Additional map: eIF4F after focus 4F Resampled map
+Additional map: eIF4F eIF3 after focus 4F
+Additional map: eIF4F after focus 4F
+Half map: Half map1 48S
+Half map: Half map1 48S
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Sample components
+Entire : Human 48S translation initiation complex
+Supramolecule #1: Human 48S translation initiation complex
+Macromolecule #1: Eukaryotic translation initiation factor 3 subunit E
+Macromolecule #2: Eukaryotic translation initiation factor 3 subunit F
+Macromolecule #3: Eukaryotic translation initiation factor 3 subunit G
+Macromolecule #4: Eukaryotic translation initiation factor 3 subunit H
+Macromolecule #5: 60S ribosomal protein L41
+Macromolecule #6: Eukaryotic translation initiation factor 3 subunit A
+Macromolecule #7: Eukaryotic translation initiation factor 3 subunit K
+Macromolecule #8: Eukaryotic translation initiation factor 3 subunit M
+Macromolecule #9: Eukaryotic translation initiation factor 2 subunit 1
+Macromolecule #10: Eukaryotic translation initiation factor 2 subunit 3
+Macromolecule #11: Eukaryotic translation initiation factor 3 subunit I
+Macromolecule #12: Eukaryotic translation initiation factor 1A, X-chromosomal
+Macromolecule #13: Eukaryotic translation initiation factor 5
+Macromolecule #14: Eukaryotic translation initiation factor 3 subunit B
+Macromolecule #15: Eukaryotic translation initiation factor 3 subunit C
+Macromolecule #16: Eukaryotic translation initiation factor 3 subunit L
+Macromolecule #17: 40S ribosomal protein S7
+Macromolecule #18: 40S ribosomal protein S27
+Macromolecule #19: 40S ribosomal protein S21
+Macromolecule #20: 40S ribosomal protein S2
+Macromolecule #21: 40S ribosomal protein S3a
+Macromolecule #22: 40S ribosomal protein SA
+Macromolecule #23: 40S ribosomal protein S26
+Macromolecule #24: 40S ribosomal protein S6
+Macromolecule #25: 40S ribosomal protein S14
+Macromolecule #26: Eukaryotic translation initiation factor 2 subunit 2
+Macromolecule #27: 40S ribosomal protein S13
+Macromolecule #29: 40S ribosomal protein S11
+Macromolecule #30: 40S ribosomal protein S4, X isoform
+Macromolecule #31: 40S ribosomal protein S9
+Macromolecule #32: 40S ribosomal protein S23
+Macromolecule #33: 40S ribosomal protein S30
+Macromolecule #34: 40S ribosomal protein S15a
+Macromolecule #35: 40S ribosomal protein S8
+Macromolecule #36: 40S ribosomal protein S24
+Macromolecule #37: 40S ribosomal protein S5
+Macromolecule #38: 40S ribosomal protein S16
+Macromolecule #39: 40S ribosomal protein S3
+Macromolecule #40: 40S ribosomal protein S10
+Macromolecule #41: 40S ribosomal protein S15
+Macromolecule #42: Receptor of activated protein C kinase 1
+Macromolecule #43: 40S ribosomal protein S19
+Macromolecule #44: 40S ribosomal protein S25
+Macromolecule #45: Small ribosomal subunit protein uS13
+Macromolecule #46: 40S ribosomal protein S29
+Macromolecule #47: Ubiquitin-40S ribosomal protein S27a
+Macromolecule #48: 40S ribosomal protein S12
+Macromolecule #49: 40S ribosomal protein S28
+Macromolecule #50: 40S ribosomal protein S17
+Macromolecule #51: 40S ribosomal protein S20
+Macromolecule #52: Eukaryotic translation initiation factor 3 subunit D
+Macromolecule #55: Eukaryotic initiation factor 4A-I
+Macromolecule #56: Eukaryotic translation initiation factor 4 gamma 1
+Macromolecule #28: 18S rRNA
+Macromolecule #53: tRNAiMet
+Macromolecule #54: mRNA
+Macromolecule #57: ZINC ION
+Macromolecule #58: MAGNESIUM 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: 7.4 |
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Grid | Model: UltrAuFoil R1.2/1.3 / Support film - Material: GRAPHENE OXIDE / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Software | Name: EPU |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 47.88 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.2 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |