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Yorodumi- EMDB-17297: Structure of a human 48S translation initiation complex with eIF4... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-17297 | ||||||||||||
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Title | Structure of a human 48S translation initiation complex with eIF4F and eIF4A | ||||||||||||
Map data | Human 48S complex | ||||||||||||
Sample |
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Keywords | translation / eIF4A / eIF4F / initiation / ribosome / mRNA | ||||||||||||
Function / homology | Function and homology information positive regulation of eukaryotic translation initiation factor 4F complex assembly / positive regulation of mRNA cap binding / male germ cell proliferation / eukaryotic initiation factor eIF2 binding / positive regulation of mRNA binding / regulation of translation in response to endoplasmic reticulum stress / translation initiation ternary complex / glial limiting end-foot / macromolecule biosynthetic process / positive regulation of translation in response to endoplasmic reticulum stress ...positive regulation of eukaryotic translation initiation factor 4F complex assembly / positive regulation of mRNA cap binding / male germ cell proliferation / eukaryotic initiation factor eIF2 binding / positive regulation of mRNA binding / regulation of translation in response to endoplasmic reticulum stress / translation initiation ternary complex / glial limiting end-foot / macromolecule biosynthetic process / positive regulation of translation in response to endoplasmic reticulum stress / HRI-mediated signaling / response to kainic acid / Cellular response to mitochondrial stress / viral translational termination-reinitiation / response to manganese-induced endoplasmic reticulum stress / positive regulation of type B pancreatic cell apoptotic process / negative regulation of translational initiation in response to stress / eukaryotic translation initiation factor 3 complex, eIF3e / Response of EIF2AK1 (HRI) to heme deficiency / regulation of cellular response to stress / Recycling of eIF2:GDP / Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / cap-dependent translational initiation / eukaryotic translation initiation factor 3 complex, eIF3m / PERK-mediated unfolded protein response / methionyl-initiator methionine tRNA binding / eukaryotic initiation factor 4E binding / PERK regulates gene expression / IRES-dependent viral translational initiation / translation reinitiation / regulation of translational initiation in response to stress / eukaryotic translation initiation factor 2 complex / RNA cap binding / nuclear stress granule / eukaryotic translation initiation factor 3 complex / eukaryotic translation initiation factor 4F complex / formation of cytoplasmic translation initiation complex / multi-eIF complex / Z-decay: degradation of maternal mRNAs by zygotically expressed factors / cytoplasmic translational initiation / translation factor activity, RNA binding / protein-synthesizing GTPase / mRNA cap binding / eukaryotic 43S preinitiation complex / formation of translation preinitiation complex / Deadenylation of mRNA / miRNA-mediated gene silencing by inhibition of translation / : / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein tyrosine kinase inhibitor activity / positive regulation of respiratory burst involved in inflammatory response / eukaryotic 48S preinitiation complex / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / nucleolus organization / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / M-decay: degradation of maternal mRNAs by maternally stored factors / 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 / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / supercoiled DNA binding / positive regulation of protein localization to cell periphery / oxidized purine DNA binding / neural crest cell differentiation / GDP-dissociation inhibitor activity / NF-kappaB complex / ubiquitin-like protein conjugating enzyme binding / regulation of translational initiation / regulation of establishment of cell polarity / positive regulation of ubiquitin-protein transferase activity / negative regulation of phagocytosis / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / Formation of the ternary complex, and subsequently, the 43S complex / cytoplasmic side of rough endoplasmic reticulum membrane / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / laminin receptor activity / pigmentation / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / Translation initiation complex formation / mammalian oogenesis stage / fibroblast growth factor binding / positive regulation of mitochondrial depolarization / activation-induced cell death of T cells / positive regulation of T cell receptor signaling pathway / negative regulation of peptidyl-serine phosphorylation / iron-sulfur cluster binding / negative regulation of Wnt signaling pathway / negative regulation of peptidyl-threonine phosphorylation Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||||||||
Authors | Brito Querido J / Sokabe M / Diaz-Lopez I / Gordiyenko Y / Fraser CS / Ramakrishnan V | ||||||||||||
Funding support | United Kingdom, United States, 3 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2024 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 | emd_17297.map.gz | 32.6 MB | EMDB map data format | |
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Header (meta data) | emd-17297-v30.xml emd-17297.xml | 108.8 KB 108.8 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_17297_fsc.xml | 14.2 KB | Display | FSC data file |
Images | emd_17297.png | 85.4 KB | ||
Masks | emd_17297_msk_1.map | 244.1 MB | Mask map | |
Filedesc metadata | emd-17297.cif.gz | 20.8 KB | ||
Others | emd_17297_additional_1.map.gz emd_17297_additional_10.map.gz emd_17297_additional_11.map.gz emd_17297_additional_2.map.gz emd_17297_additional_3.map.gz emd_17297_additional_4.map.gz emd_17297_additional_5.map.gz emd_17297_additional_6.map.gz emd_17297_additional_7.map.gz emd_17297_additional_8.map.gz emd_17297_additional_9.map.gz emd_17297_half_map_1.map.gz emd_17297_half_map_2.map.gz | 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 | http://ftp.pdbj.org/pub/emdb/structures/EMD-17297 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-17297 | HTTPS FTP |
-Validation report
Summary document | emd_17297_validation.pdf.gz | 1.1 MB | Display | EMDB validaton report |
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Full document | emd_17297_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | emd_17297_validation.xml.gz | 22.5 KB | Display | |
Data in CIF | emd_17297_validation.cif.gz | 28.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-17297 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-17297 | HTTPS FTP |
-Related structure data
Related structure data | 8oz0MC M: atomic model generated by this map C: citing same article (ref.) |
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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_17297.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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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
-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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Processing | single particle reconstruction |
Aggregation state | particle |
-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 |
-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: FIELD EMISSION GUN |
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 |