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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 / positive regulation of mRNA cap binding / eukaryotic initiation factor eIF2 binding / male germ cell proliferation / positive regulation of mRNA binding / regulation of translation in response to endoplasmic reticulum stress / translation initiation ternary complex / glial limiting end-foot / response to kainic acid / viral translational termination-reinitiation ...positive regulation of eukaryotic translation initiation factor 4F complex assembly / positive regulation of mRNA cap binding / eukaryotic initiation factor eIF2 binding / male germ cell proliferation / positive regulation of mRNA binding / regulation of translation in response to endoplasmic reticulum stress / translation initiation ternary complex / glial limiting end-foot / response to kainic acid / viral translational termination-reinitiation / Cellular response to mitochondrial stress / positive regulation of translation in response to endoplasmic reticulum stress / response to manganese-induced endoplasmic reticulum stress / eukaryotic translation initiation factor 3 complex, eIF3e / positive regulation of type B pancreatic cell apoptotic process / methionyl-initiator methionine tRNA binding / cap-dependent translational initiation / eukaryotic translation initiation factor 3 complex, eIF3m / negative regulation of translational initiation in response to stress / Response of EIF2AK1 (HRI) to heme deficiency / macromolecule biosynthetic process / Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / Recycling of eIF2:GDP / translation reinitiation / PERK-mediated unfolded protein response / regulation of cellular response to stress / eukaryotic initiation factor 4E binding / IRES-dependent viral translational initiation / PERK regulates gene expression / eukaryotic translation initiation factor 2 complex / regulation of translational initiation in response to stress / Z-decay: degradation of maternal mRNAs by zygotically expressed factors / multi-eIF complex / eukaryotic translation initiation factor 3 complex / selenocysteine metabolic process / RNA cap binding / eukaryotic translation initiation factor 4F complex / selenocysteine incorporation / eukaryotic 43S preinitiation complex / protein-synthesizing GTPase / cytoplasmic translational initiation / Deadenylation of mRNA / translation factor activity, RNA binding / mRNA cap binding / formation of cytoplasmic translation initiation complex / selenocysteine insertion sequence binding / formation of translation preinitiation complex / miRNA-mediated gene silencing by inhibition of translation / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / eukaryotic 48S preinitiation complex / response to TNF agonist / positive regulation of base-excision repair / protein tyrosine kinase inhibitor activity / positive regulation of respiratory burst involved in inflammatory response / M-decay: degradation of maternal mRNAs by maternally stored factors / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / nucleolus organization / IRE1-RACK1-PP2A complex / : / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / negative regulation of RNA splicing / negative regulation of DNA repair / metal-dependent deubiquitinase activity / positive regulation of protein localization to cell periphery / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / oxidized purine DNA binding / supercoiled DNA binding / neural crest cell differentiation / NF-kappaB complex / GDP-dissociation inhibitor activity / ubiquitin-like protein conjugating enzyme binding / regulation of translational initiation / regulation of establishment of cell polarity / negative regulation of phagocytosis / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / protein kinase A binding / Translation initiation complex formation / Ribosomal scanning and start codon recognition / negative regulation of ubiquitin protein ligase activity / ion channel inhibitor activity / pigmentation / mammalian oogenesis stage / positive regulation of mitochondrial depolarization / activation-induced cell death of T cells / negative regulation of Wnt signaling pathway / fibroblast growth factor binding / 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 |
-Validation report
Summary document | ![]() | 1.1 MB | Display | ![]() |
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Full document | ![]() | 1.1 MB | Display | |
Data in XML | ![]() | 22.5 KB | Display | |
Data in CIF | ![]() | 28.5 KB | Display | |
Arichive 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
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Annotation | Human 48S complex | ||||||||||||||||||||
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 |