[English] 日本語
Yorodumi- PDB-7rlo: Structure of the human eukaryotic translation initiation factor 2... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7rlo | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of the human eukaryotic translation initiation factor 2B (eIF2B) in complex with a viral protein NSs | ||||||
Components |
| ||||||
Keywords | TRANSLATION / Complex / viral protein / integrated stress response / protein translation | ||||||
Function / homology | Function and homology information eukaryotic translation initiation factor 2B complex / Recycling of eIF2:GDP / cytoplasmic translational initiation / guanyl-nucleotide exchange factor complex / oligodendrocyte development / astrocyte development / astrocyte differentiation / regulation of translational initiation / positive regulation of translational initiation / response to glucose ...eukaryotic translation initiation factor 2B complex / Recycling of eIF2:GDP / cytoplasmic translational initiation / guanyl-nucleotide exchange factor complex / oligodendrocyte development / astrocyte development / astrocyte differentiation / regulation of translational initiation / positive regulation of translational initiation / response to glucose / ovarian follicle development / translation initiation factor binding / response to endoplasmic reticulum stress / myelination / translation initiation factor activity / guanyl-nucleotide exchange factor activity / central nervous system development / hippocampus development / translational initiation / response to peptide hormone / regulation of translation / T cell receptor signaling pathway / response to heat / positive regulation of apoptotic process / GTP binding / ATP binding / identical protein binding / membrane / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) Sandfly fever sicilian virus | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.6 Å | ||||||
Authors | Wang, L. / Schoof, M. / Cogan, J. / Lawrence, R. / Boone, M. / Wuerth, J. / Frost, M. / Walter, P. | ||||||
Funding support | United States, 1items
| ||||||
Citation | Journal: Nat Commun / Year: 2021 Title: Viral evasion of the integrated stress response through antagonism of eIF2-P binding to eIF2B. Authors: Michael Schoof / Lan Wang / J Zachery Cogan / Rosalie E Lawrence / Morgane Boone / Jennifer Deborah Wuerth / Adam Frost / Peter Walter / Abstract: Viral infection triggers activation of the integrated stress response (ISR). In response to viral double-stranded RNA (dsRNA), RNA-activated protein kinase (PKR) phosphorylates the translation ...Viral infection triggers activation of the integrated stress response (ISR). In response to viral double-stranded RNA (dsRNA), RNA-activated protein kinase (PKR) phosphorylates the translation initiation factor eIF2, converting it from a translation initiator into a potent translation inhibitor and this restricts the synthesis of viral proteins. Phosphorylated eIF2 (eIF2-P) inhibits translation by binding to eIF2's dedicated, heterodecameric nucleotide exchange factor eIF2B and conformationally inactivating it. We show that the NSs protein of Sandfly Fever Sicilian virus (SFSV) allows the virus to evade the ISR. Mechanistically, NSs tightly binds to eIF2B (K= 30 nM), blocks eIF2-P binding, and rescues eIF2B GEF activity. Cryo-EM structures demonstrate that SFSV NSs and eIF2-P directly compete, with the primary NSs contacts to eIF2Bα mediated by five 'aromatic fingers'. NSs binding preserves eIF2B activity by maintaining eIF2B's conformation in its active A-State. | ||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7rlo.cif.gz | 661 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7rlo.ent.gz | 521.6 KB | Display | PDB format |
PDBx/mmJSON format | 7rlo.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7rlo_validation.pdf.gz | 981.2 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 7rlo_full_validation.pdf.gz | 1019.5 KB | Display | |
Data in XML | 7rlo_validation.xml.gz | 88.9 KB | Display | |
Data in CIF | 7rlo_validation.cif.gz | 137.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rl/7rlo ftp://data.pdbj.org/pub/pdb/validation_reports/rl/7rlo | HTTPS FTP |
-Related structure data
Related structure data | 24535MC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Translation initiation factor eIF-2B subunit ... , 5 types, 10 molecules ABCDEFGHIJ
#1: Protein | Mass: 80466.609 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EIF2B5, EIF2BE / Production host: Escherichia coli (E. coli) / References: UniProt: Q13144 #2: Protein | Mass: 39039.547 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EIF2B2, EIF2BB / Production host: Escherichia coli (E. coli) / References: UniProt: P49770 #3: Protein | Mass: 57640.168 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EIF2B4, EIF2BD / Production host: Escherichia coli (E. coli) / References: UniProt: Q9UI10 #4: Protein | Mass: 33754.148 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EIF2B1, EIF2BA / Production host: Escherichia coli (E. coli) / References: UniProt: Q14232 #5: Protein | Mass: 50304.230 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EIF2B3 / Production host: Escherichia coli (E. coli) / References: UniProt: Q9NR50 |
---|
-Protein , 1 types, 2 molecules KL
#6: Protein | Mass: 30668.383 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Sandfly fever sicilian virus / Gene: NSS / Production host: Homo sapiens (human) / References: UniProt: P12792 |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular weight |
| ||||||||||||||||||||||||
Source (natural) |
| ||||||||||||||||||||||||
Source (recombinant) |
| ||||||||||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 67 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 137093 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 99.74 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
|