[English] 日本語
Yorodumi
- PDB-7f64: eIF2B-SFSV NSs -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7f64
TitleeIF2B-SFSV NSs
Components
  • (Translation initiation factor eIF-2B subunit ...) x 5
  • Non-structural protein NS-S
KeywordsTRANSLATION / translation initiation factor / viral protein
Function / homology
Function and homology information


eukaryotic translation initiation factor 2B complex / Recycling of eIF2:GDP / cytoplasmic translational initiation / oligodendrocyte development / guanyl-nucleotide exchange factor complex / 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 / oligodendrocyte development / guanyl-nucleotide exchange factor complex / astrocyte development / astrocyte differentiation / regulation of translational initiation / positive regulation of translational initiation / response to glucose / ovarian follicle development / translation initiation factor binding / translational initiation / translation initiation factor activity / myelination / response to endoplasmic reticulum stress / guanyl-nucleotide exchange factor activity / central nervous system development / hippocampus development / response to peptide hormone / regulation of translation / T cell receptor signaling pathway / response to heat / positive regulation of apoptotic process / GTP binding / ATP binding / membrane / identical protein binding / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Phlebovirus, non structural protein / Rift valley fever virus non structural protein-like / Rift valley fever virus non structural protein (NSs) like / Translation initiation factor eIF-2B subunit alpha, N-terminal / Translation initiation factor eIF-2B subunit epsilon, N-terminal / Translation initiation factor eIF-2B subunit epsilon, W2 domain / Initiation factor 2B-related / Initiation factor 2B-like, C-terminal / Initiation factor 2 subunit family / eIF4-gamma/eIF5/eIF2-epsilon ...Phlebovirus, non structural protein / Rift valley fever virus non structural protein-like / Rift valley fever virus non structural protein (NSs) like / Translation initiation factor eIF-2B subunit alpha, N-terminal / Translation initiation factor eIF-2B subunit epsilon, N-terminal / Translation initiation factor eIF-2B subunit epsilon, W2 domain / Initiation factor 2B-related / Initiation factor 2B-like, C-terminal / Initiation factor 2 subunit family / eIF4-gamma/eIF5/eIF2-epsilon / Domain at the C-termini of GCD6, eIF-2B epsilon, eIF-4 gamma and eIF-5 / W2 domain / W2 domain profile. / Nucleotidyl transferase domain / Nucleotidyl transferase / NagB/RpiA transferase-like / Trimeric LpxA-like superfamily / Nucleotide-diphospho-sugar transferases / Armadillo-type fold
Similarity search - Domain/homology
Non-structural protein NS-S / Translation initiation factor eIF2B subunit beta / Translation initiation factor eIF2B subunit epsilon / Translation initiation factor eIF2B subunit alpha / Translation initiation factor eIF2B subunit gamma / Translation initiation factor eIF2B subunit delta
Similarity search - Component
Biological speciesHomo sapiens (human)
Sandfly fever sicilian virus
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.42 Å
AuthorsKashiwagi, K. / Ito, T.
Funding support Japan, 3items
OrganizationGrant numberCountry
Japan Society for the Promotion of Science (JSPS)JP19H03172 Japan
Japan Agency for Medical Research and Development (AMED)JP21gm1410001 Japan
Japan Society for the Promotion of Science (JSPS)JP18K14644 Japan
CitationJournal: 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
DepositionJun 24, 2021Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Dec 8, 2021Provider: repository / Type: Initial release
Revision 1.1Feb 16, 2022Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Jun 12, 2024Group: Data collection / Category: chem_comp_atom / chem_comp_bond

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-31472
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Translation initiation factor eIF-2B subunit alpha
B: Translation initiation factor eIF-2B subunit alpha
C: Translation initiation factor eIF-2B subunit beta
D: Translation initiation factor eIF-2B subunit beta
E: Translation initiation factor eIF-2B subunit gamma
F: Translation initiation factor eIF-2B subunit gamma
G: Translation initiation factor eIF-2B subunit delta
H: Translation initiation factor eIF-2B subunit delta
I: Translation initiation factor eIF-2B subunit epsilon
J: Translation initiation factor eIF-2B subunit epsilon
K: Non-structural protein NS-S
L: Non-structural protein NS-S


Theoretical massNumber of molelcules
Total (without water)581,80012
Polymers581,80012
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

-
Translation initiation factor eIF-2B subunit ... , 5 types, 10 molecules ABCDEFGHIJ

#1: Protein Translation initiation factor eIF-2B subunit alpha / eIF-2B GDP-GTP exchange factor subunit alpha


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
#2: Protein Translation initiation factor eIF-2B subunit beta / S20I15 / S20III15 / eIF-2B GDP-GTP exchange factor subunit beta


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 Translation initiation factor eIF-2B subunit gamma / eIF2Bg / eIF-2B GDP-GTP exchange factor subunit gamma


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
#4: Protein Translation initiation factor eIF-2B subunit delta / eIF-2B GDP-GTP exchange factor subunit delta


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
#5: Protein Translation initiation factor eIF-2B subunit epsilon / eIF-2B GDP-GTP exchange factor subunit epsilon


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

-
Protein , 1 types, 2 molecules KL

#6: Protein Non-structural protein NS-S


Mass: 29695.385 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Sandfly fever sicilian virus / Gene: NSS / Production host: Escherichia coli (E. coli) / References: UniProt: P12792

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

Component
IDNameTypeEntity IDParent-IDSource
1Complex of eIF2B and SFSV NSsCOMPLEXall0MULTIPLE SOURCES
2eIF2BCOMPLEX#1-#51RECOMBINANT
3SFSV NSsCOMPLEX#61RECOMBINANT
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
12Homo sapiens (human)9606
23Sandfly fever sicilian virus28292
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-ID
12Escherichia coli (E. coli)562
23Escherichia coli (E. coli)562
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

-
Processing

SoftwareName: PHENIX / Version: 1.19.2_4158: / Classification: refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.42 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 888479 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00229292
ELECTRON MICROSCOPYf_angle_d0.5239700
ELECTRON MICROSCOPYf_dihedral_angle_d4.053998
ELECTRON MICROSCOPYf_chiral_restr0.0424634
ELECTRON MICROSCOPYf_plane_restr0.0045072

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbjlvh1.pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more