+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31475 | ||||||||||||
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Title | eIF2B-SFSV NSs-2-eIF2 | ||||||||||||
Map data | |||||||||||||
Sample |
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Keywords | translation initiation factor / viral protein / TRANSLATION | ||||||||||||
Function / homology | Function and homology information regulation of translation in response to endoplasmic reticulum stress / translation initiation ternary complex / glial limiting end-foot / response to kainic acid / HRI-mediated signaling / Cellular response to mitochondrial stress / eukaryotic translation initiation factor 2B complex / response to manganese-induced endoplasmic reticulum stress / positive regulation of type B pancreatic cell apoptotic process / methionyl-initiator methionine tRNA binding ...regulation of translation in response to endoplasmic reticulum stress / translation initiation ternary complex / glial limiting end-foot / response to kainic acid / HRI-mediated signaling / Cellular response to mitochondrial stress / eukaryotic translation initiation factor 2B complex / response to manganese-induced endoplasmic reticulum stress / positive regulation of type B pancreatic cell apoptotic process / methionyl-initiator methionine tRNA binding / negative regulation of translational initiation in response to stress / Response of EIF2AK1 (HRI) to heme deficiency / Recycling of eIF2:GDP / PERK-mediated unfolded protein response / PERK regulates gene expression / eukaryotic translation initiation factor 2 complex / regulation of translational initiation in response to stress / protein-synthesizing GTPase / cytoplasmic translational initiation / translation factor activity, RNA binding / formation of translation preinitiation complex / oligodendrocyte development / guanyl-nucleotide exchange factor complex / astrocyte development / eukaryotic 48S preinitiation complex / astrocyte differentiation / regulation of translational initiation / Formation of the ternary complex, and subsequently, the 43S complex / Ribosomal scanning and start codon recognition / Translation initiation complex formation / Response of EIF2AK4 (GCN2) to amino acid deficiency / mitophagy / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / positive regulation of translational initiation / response to glucose / stress granule assembly / ovarian follicle development / translation initiation factor binding / myelination / translation initiation factor activity / cellular response to amino acid starvation / response to endoplasmic reticulum stress / guanyl-nucleotide exchange factor activity / central nervous system development / translational initiation / hippocampus development / PKR-mediated signaling / ABC-family proteins mediated transport / response to peptide hormone / cytoplasmic stress granule / cellular response to UV / ribosome binding / regulation of translation / T cell receptor signaling pathway / cellular response to oxidative stress / cellular response to heat / response to heat / cadherin binding / positive regulation of apoptotic process / GTPase activity / synapse / GTP binding / mitochondrion / RNA binding / extracellular exosome / ATP binding / identical protein binding / membrane / nucleus / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) / Sandfly fever sicilian virus | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.59 Å | ||||||||||||
Authors | Kashiwagi K / Ito T | ||||||||||||
Funding support | Japan, 3 items
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Citation | Journal: Nat Commun / Year: 2021 Title: eIF2B-capturing viral protein NSs suppresses the integrated stress response. Authors: Kazuhiro Kashiwagi / Yuichi Shichino / Tatsuya Osaki / Ayako Sakamoto / Madoka Nishimoto / Mari Takahashi / Mari Mito / Friedemann Weber / Yoshiho Ikeuchi / Shintaro Iwasaki / Takuhiro Ito / Abstract: Various stressors such as viral infection lead to the suppression of cap-dependent translation and the activation of the integrated stress response (ISR), since the stress-induced phosphorylated ...Various stressors such as viral infection lead to the suppression of cap-dependent translation and the activation of the integrated stress response (ISR), since the stress-induced phosphorylated eukaryotic translation initiation factor 2 [eIF2(αP)] tightly binds to eIF2B to prevent it from exchanging guanine nucleotide molecules on its substrate, unphosphorylated eIF2. Sandfly fever Sicilian virus (SFSV) evades this cap-dependent translation suppression through the interaction between its nonstructural protein NSs and host eIF2B. However, its precise mechanism has remained unclear. Here, our cryo-electron microscopy (cryo-EM) analysis reveals that SFSV NSs binds to the α-subunit of eIF2B in a competitive manner with eIF2(αP). Together with SFSV NSs, eIF2B retains nucleotide exchange activity even in the presence of eIF2(αP), in line with the cryo-EM structures of the eIF2B•SFSV NSs•unphosphorylated eIF2 complex. A genome-wide ribosome profiling analysis clarified that SFSV NSs expressed in cultured human cells attenuates the ISR triggered by thapsigargin, an endoplasmic reticulum stress inducer. Furthermore, SFSV NSs introduced in rat hippocampal neurons and human induced-pluripotent stem (iPS) cell-derived motor neurons exhibits neuroprotective effects against the ISR-inducing stress. Since ISR inhibition is beneficial in various neurological disease models, SFSV NSs may be a promising therapeutic ISR inhibitor. | ||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_31475.map.gz | 208.1 MB | EMDB map data format | |
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Header (meta data) | emd-31475-v30.xml emd-31475.xml | 22.7 KB 22.7 KB | Display Display | EMDB header |
Images | emd_31475.png | 94.5 KB | ||
Filedesc metadata | emd-31475.cif.gz | 7.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31475 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31475 | HTTPS FTP |
-Validation report
Summary document | emd_31475_validation.pdf.gz | 388.8 KB | Display | EMDB validaton report |
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Full document | emd_31475_full_validation.pdf.gz | 388.4 KB | Display | |
Data in XML | emd_31475_validation.xml.gz | 7.7 KB | Display | |
Data in CIF | emd_31475_validation.cif.gz | 8.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31475 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31475 | HTTPS FTP |
-Related structure data
Related structure data | 7f67MC 7f64C 7f66C 7vlkC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_31475.map.gz / Format: CCP4 / Size: 347.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 0.829 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
+Entire : Complex of eIF2B, eIF2, and SFSV NSs
+Supramolecule #1: Complex of eIF2B, eIF2, and SFSV NSs
+Supramolecule #2: eIF2B, eIF2
+Supramolecule #3: SFSV NSs
+Macromolecule #1: Translation initiation factor eIF-2B subunit alpha
+Macromolecule #2: Translation initiation factor eIF-2B subunit beta
+Macromolecule #3: Translation initiation factor eIF-2B subunit gamma
+Macromolecule #4: Translation initiation factor eIF-2B subunit delta
+Macromolecule #5: Translation initiation factor eIF-2B subunit epsilon
+Macromolecule #6: Non-structural protein NS-S
+Macromolecule #7: Eukaryotic translation initiation factor 2 subunit 1
+Macromolecule #8: eIF2beta
+Macromolecule #9: Eukaryotic translation initiation factor 2 subunit 3
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: EMDB MAP |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.59 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 8106 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |