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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-31475 | ||||||||||||
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Title | eIF2B-SFSV NSs-2-eIF2 | ||||||||||||
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![]() | translation initiation factor / viral protein / TRANSLATION | ||||||||||||
Function / homology | ![]() regulation of translation in response to endoplasmic reticulum stress / translation initiation ternary complex / glial limiting end-foot / response to kainic acid / Cellular response to mitochondrial stress / response to manganese-induced endoplasmic reticulum stress / positive regulation of type B pancreatic cell apoptotic process / methionyl-initiator methionine tRNA binding / eukaryotic translation initiation factor 2B complex / negative regulation of translational initiation in response to stress ...regulation of translation in response to endoplasmic reticulum stress / translation initiation ternary complex / glial limiting end-foot / response to kainic acid / Cellular response to mitochondrial stress / response to manganese-induced endoplasmic reticulum stress / positive regulation of type B pancreatic cell apoptotic process / methionyl-initiator methionine tRNA binding / eukaryotic translation initiation factor 2B complex / 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 / selenocysteine metabolic process / selenocysteine incorporation / protein-synthesizing GTPase / cytoplasmic translational initiation / translation factor activity, RNA binding / oligodendrocyte development / selenocysteine insertion sequence binding / formation of translation preinitiation complex / guanyl-nucleotide exchange factor complex / astrocyte development / eukaryotic 48S preinitiation complex / astrocyte differentiation / Formation of the ternary complex, and subsequently, the 43S complex / regulation of translational initiation / Translation initiation complex formation / Ribosomal scanning and start codon recognition / Response of EIF2AK4 (GCN2) to amino acid deficiency / L13a-mediated translational silencing of Ceruloplasmin expression / GTP hydrolysis and joining of the 60S ribosomal subunit / positive regulation of translational initiation / response to glucose / stress granule assembly / ovarian follicle development / translation initiation factor binding / translational initiation / translation initiation factor activity / cellular response to amino acid starvation / myelination / response to endoplasmic reticulum stress / guanyl-nucleotide exchange factor activity / central nervous system development / hippocampus development / ABC-family proteins mediated transport / PKR-mediated signaling / response to peptide hormone / cytoplasmic stress granule / cellular response to UV / ribosome binding / regulation of translation / T cell receptor signaling pathway / cellular response to heat / cellular response to oxidative stress / response to heat / cadherin binding / positive regulation of apoptotic process / GTPase activity / synapse / GTP binding / RNA binding / extracellular exosome / ATP binding / membrane / identical protein binding / nucleus / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.59 Å | ||||||||||||
![]() | Kashiwagi K / Ito T | ||||||||||||
Funding support | ![]()
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![]() | ![]() 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
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 208.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 22.7 KB 22.7 KB | Display Display | ![]() |
Images | ![]() | 94.5 KB | ||
Filedesc metadata | ![]() | 7.6 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 388.8 KB | Display | ![]() |
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Full document | ![]() | 388.4 KB | Display | |
Data in XML | ![]() | 7.7 KB | Display | |
Data in CIF | ![]() | 8.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7f67MC ![]() 7f64C ![]() 7f66C ![]() 7vlkC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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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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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
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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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![]() | 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 | 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: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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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 |