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Open data
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Basic information
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| Title | human 48S PIC with mRNA (non-Kozak) | |||||||||
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Keywords | translation initiation / Kozak sequence / RIBOSOME | |||||||||
| Function / homology | Function and homology informationtranslation initiation ternary complex / regulation of translation in response to endoplasmic reticulum stress / glial limiting end-foot / response to manganese-induced endoplasmic reticulum stress / Cellular response to mitochondrial stress / positive regulation of type B pancreatic cell apoptotic process / HRI-mediated signaling / methionyl-initiator methionine tRNA binding / Response of EIF2AK1 (HRI) to heme deficiency / negative regulation of translational initiation in response to stress ...translation initiation ternary complex / regulation of translation in response to endoplasmic reticulum stress / glial limiting end-foot / response to manganese-induced endoplasmic reticulum stress / Cellular response to mitochondrial stress / positive regulation of type B pancreatic cell apoptotic process / HRI-mediated signaling / methionyl-initiator methionine tRNA binding / Response of EIF2AK1 (HRI) to heme deficiency / negative regulation of translational initiation in response to stress / PERK-mediated unfolded protein response / Recycling of eIF2:GDP / PERK regulates gene expression / response to kainic acid / eukaryotic translation initiation factor 2 complex / multi-eIF complex / regulation of translational initiation in response to stress / eukaryotic 43S preinitiation complex / translation factor activity, RNA binding / formation of translation preinitiation complex / 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 / protein-synthesizing GTPase / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / protein tyrosine kinase inhibitor activity / regulation of translational initiation / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / nucleolus organization / TNFR1-mediated ceramide production / positive regulation of ubiquitin-protein transferase activity / positive regulation of DNA-templated transcription initiation / negative regulation of RNA splicing / negative regulation of DNA repair / erythrocyte homeostasis / supercoiled DNA binding / regulation of establishment of cell polarity / cysteine-type endopeptidase activator activity involved in apoptotic process / oxidized purine DNA binding / NF-kappaB complex / cytoplasmic translational initiation / rRNA modification in the nucleus and cytosol / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / negative regulation of phagocytosis / negative regulation of bicellular tight junction assembly / ubiquitin-like protein conjugating enzyme binding / cytoplasmic side of rough endoplasmic reticulum membrane / Formation of the ternary complex, and subsequently, the 43S complex / laminin receptor activity / negative regulation of myoblast fusion / ion channel inhibitor activity / protein kinase A binding / positive regulation of mitochondrial depolarization / Ribosomal scanning and start codon recognition / PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA / Translation initiation complex formation / negative regulation of Wnt signaling pathway / fibroblast growth factor binding / ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA / Protein hydroxylation / TOR signaling / BH3 domain binding / negative regulation of translational frameshifting / iron-sulfur cluster binding / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / monocyte chemotaxis / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / regulation of cell division / positive regulation of GTPase activity / Peptide chain elongation / cellular response to ethanol / Dengue Virus Attachment and Entry / Selenocysteine synthesis / Formation of a pool of free 40S subunits / negative regulation of protein binding / negative regulation of respiratory burst involved in inflammatory response / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Eukaryotic Translation Termination / protein serine/threonine kinase inhibitor activity / SRP-dependent cotranslational protein targeting to membrane / Response of EIF2AK4 (GCN2) to amino acid deficiency / negative regulation of ubiquitin-dependent protein catabolic process / ubiquitin ligase inhibitor activity / Viral mRNA Translation / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / positive regulation of signal transduction by p53 class mediator / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / mitophagy / Major pathway of rRNA processing in the nucleolus and cytosol / regulation of translational fidelity / positive regulation of microtubule polymerization / phagocytic cup Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||
Authors | von Loeffelholz O / Barchet C / Klaholz B | |||||||||
| Funding support | France, 1 items
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Citation | Journal: Nat Commun / Year: 2026Title: Translation initiation by the Kozak mRNA sequence is based on a conformational readout on the ribosome. Authors: Ottilie von Loeffelholz / Charles Barchet / Samuel Holvec / Aida Abou Ramadan / Cristina Protuc / Anne Maglott-Roth / S Nimali T de Silva / Isabelle Hazemann / Bruno P Klaholz / ![]() Abstract: The recognition mechanism of Kozak mRNA, typically comprising purines in the -3 and +4 positions flanking the AUG start codon, has remained enigmatic for decades. To address this fundamental function ...The recognition mechanism of Kozak mRNA, typically comprising purines in the -3 and +4 positions flanking the AUG start codon, has remained enigmatic for decades. To address this fundamental function in eukaryotes during translation initiation, we analysed several cryo-EM structures of human 48S preinitiation complexes with mRNA sequences differing in Kozak activity revealing distinct modes of recognition. The pre-codon triplet forms a fan-like intercalation into the 18S ribosomal RNA (rRNA), while a -3 pyrimidine destabilizes ternary complex positioning. Specificity towards the +4 purine is achieved beyond a single residue recognition by mutual conformational adaptations of eIF1A, mRNA and rRNA that involve the insertion of a reading head in which decoding residue A1825 (rRNA) stacks with the A-site codon to stabilize the fully accommodated state. Hence, instead of relying on base pairing as in bacteria, the specific recognition of the Kozak sequence on eukaryotic ribosomes is based on an induced-fit mechanism that triggers a conformational readout of the mRNA. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_57005.map.gz | 496 MB | EMDB map data format | |
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| Header (meta data) | emd-57005-v30.xml emd-57005.xml | 60.3 KB 60.3 KB | Display Display | EMDB header |
| Images | emd_57005.png | 47.8 KB | ||
| Filedesc metadata | emd-57005.cif.gz | 14.4 KB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-57005 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-57005 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 28zvMC ![]() 28zuC ![]() 28zxC ![]() 28zyC C: citing same article ( M: atomic model generated by this map |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_57005.map.gz / Format: CCP4 / Size: 536.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.72 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
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Sample components
+Entire : 48S PIC
+Supramolecule #1: 48S PIC
+Macromolecule #1: 18S ribosomal RNA
+Macromolecule #21: mRNA
+Macromolecule #40: initiator tRNA
+Macromolecule #2: 60S ribosomal protein L41
+Macromolecule #3: Small ribosomal subunit protein eS4, X isoform
+Macromolecule #4: 40S ribosomal protein SA
+Macromolecule #5: 40S ribosomal protein S3a
+Macromolecule #6: 40S ribosomal protein S7
+Macromolecule #7: 40S ribosomal protein S8
+Macromolecule #8: Small ribosomal subunit protein uS17
+Macromolecule #9: 40S ribosomal protein S21
+Macromolecule #10: 40S ribosomal protein S23
+Macromolecule #11: 40S ribosomal protein S26
+Macromolecule #12: 40S ribosomal protein S2
+Macromolecule #13: 40S ribosomal protein S6
+Macromolecule #14: 40S ribosomal protein S9
+Macromolecule #15: 40S ribosomal protein S13
+Macromolecule #16: 40S ribosomal protein S14
+Macromolecule #17: 40S ribosomal protein S15a
+Macromolecule #18: 40S ribosomal protein S24
+Macromolecule #19: 40S ribosomal protein S27
+Macromolecule #20: Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein
+Macromolecule #22: 40S ribosomal protein S3
+Macromolecule #23: 40S ribosomal protein S5
+Macromolecule #24: Ubiquitin
+Macromolecule #25: 40S ribosomal protein S17
+Macromolecule #26: 40S ribosomal protein S29
+Macromolecule #27: Receptor of activated protein C kinase 1
+Macromolecule #28: 40S ribosomal protein S28
+Macromolecule #29: 40S ribosomal protein S10
+Macromolecule #30: 40S ribosomal protein S12
+Macromolecule #31: 40S ribosomal protein S20
+Macromolecule #32: 40S ribosomal protein S16
+Macromolecule #33: 40S ribosomal protein S18
+Macromolecule #34: Small ribosomal subunit protein eS19
+Macromolecule #35: 40S ribosomal protein S15
+Macromolecule #36: Small ribosomal subunit protein eS25
+Macromolecule #37: Eukaryotic translation initiation factor 2 subunit 1
+Macromolecule #38: Eukaryotic translation initiation factor 2 subunit 3
+Macromolecule #39: Eukaryotic translation initiation factor 2 subunit 2
+Macromolecule #41: Eukaryotic translation initiation factor 1A, X-chromosomal
+Macromolecule #42: POTASSIUM ION
+Macromolecule #43: MAGNESIUM ION
+Macromolecule #44: ZINC ION
+Macromolecule #45: PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER
+Macromolecule #46: METHIONINE
+Macromolecule #47: water
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.5 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Image recording | Film or detector model: TFS FALCON 4i (4k x 4k) / Average electron dose: 40.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.5 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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About Yorodumi




Keywords
Homo sapiens (human)
Authors
France, 1 items
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Y (Row.)
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Processing
FIELD EMISSION GUN
