[English] 日本語
Yorodumi
- PDB-9mk9: Structure of the IFIT2-IFIT3 heterodimer from Mus musculus -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9mk9
TitleStructure of the IFIT2-IFIT3 heterodimer from Mus musculus
Components
  • Interferon-induced protein with tetratricopeptide repeats 2
  • Interferon-induced protein with tetratricopeptide repeats 3
KeywordsANTIVIRAL PROTEIN / innate immune recognition / interferon-induced proteins / non-self nucleic acids
Function / homology
Function and homology information


response to stilbenoid / cellular response to interferon-alpha / cellular response to interferon-beta / antiviral innate immune response / response to bacterium / response to virus / defense response to virus / positive regulation of apoptotic process / negative regulation of cell population proliferation / innate immune response ...response to stilbenoid / cellular response to interferon-alpha / cellular response to interferon-beta / antiviral innate immune response / response to bacterium / response to virus / defense response to virus / positive regulation of apoptotic process / negative regulation of cell population proliferation / innate immune response / apoptotic process / negative regulation of apoptotic process / endoplasmic reticulum / mitochondrion / RNA binding / cytoplasm
Similarity search - Function
Tetratricopeptide repeat / Tetratricopeptide repeat / TPR repeat region circular profile. / TPR repeat profile. / Tetratricopeptide repeats / Tetratricopeptide repeat / Tetratricopeptide-like helical domain superfamily
Similarity search - Domain/homology
Interferon-induced protein with tetratricopeptide repeats 2 / Interferon-induced protein with tetratricopeptide repeats 3
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.22 Å
AuthorsGlasner, D.R. / Todd, C. / Cook, B.D. / DUrso, A. / Khosla, S. / Estrada, E. / Wagner, J. / Bartels, M.D. / Ford, P. / Prych, J. ...Glasner, D.R. / Todd, C. / Cook, B.D. / DUrso, A. / Khosla, S. / Estrada, E. / Wagner, J. / Bartels, M.D. / Ford, P. / Prych, J. / Hatch, K. / Yee, B.A. / Ego, K.M. / Liang, Q. / Holland, S.R. / Case, J.B. / Corbett, K.D. / Diamond, M.S. / Yeo, G.W. / Herzik Jr., M.A. / Van Nostrand, E.L. / Daugherty, M.D.
Funding support United States, 5items
OrganizationGrant numberCountry
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)U24 HG009889 United States
National Institutes of Health/National Institute of Mental Health (NIH/NIMH)RF1 MH126719 United States
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)R01 HG011864 United States
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)National Human Genome Research Institute United States
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)U24 HG011735 United States
CitationJournal: bioRxiv / Year: 2025
Title: Short 5' UTRs serve as a marker for viral mRNA translation inhibition by the IFIT2-IFIT3 antiviral complex.
Authors: Dustin R Glasner / Candace Todd / Brian Cook / Agustina D'Urso / Shivani Khosla / Elena Estrada / Jaxon D Wagner / Mason D Bartels / Pierce Ford / Jordan Prych / Katie Hatch / Brian A Yee / ...Authors: Dustin R Glasner / Candace Todd / Brian Cook / Agustina D'Urso / Shivani Khosla / Elena Estrada / Jaxon D Wagner / Mason D Bartels / Pierce Ford / Jordan Prych / Katie Hatch / Brian A Yee / Kaori M Ego / Qishan Liang / Sarah R Holland / James Brett Case / Kevin D Corbett / Michael S Diamond / Gene W Yeo / Mark A Herzik / Eric L Van Nostrand / Matthew D Daugherty /
Abstract: Recognition of "non-self" nucleic acids, including cytoplasmic dsDNA, dsRNA, or mRNAs lacking proper 5' cap structures, is critical for the innate immune response to viruses. Here, we demonstrate ...Recognition of "non-self" nucleic acids, including cytoplasmic dsDNA, dsRNA, or mRNAs lacking proper 5' cap structures, is critical for the innate immune response to viruses. Here, we demonstrate that short 5' untranslated regions (UTRs), a characteristic of many viral mRNAs, can also serve as a molecular pattern for innate immune recognition via the interferon-induced proteins IFIT2 and IFIT3. The IFIT2-IFIT3 heterodimer, formed through an intricate domain swap structure resolved by cryo-EM, mediates viral mRNA 5' end recognition, translation inhibition, and ultimately antiviral activity. Critically, 5' UTR lengths <50 nucleotides are necessary and sufficient to sensitize an mRNA to translation inhibition by the IFIT2-IFIT3 complex. Accordingly, diverse viruses whose mRNAs contain short 5' UTRs, such as vesicular stomatitis virus and parainfluenza virus 3, are sensitive to IFIT2-IFIT3-mediated antiviral activity. Our work thus reveals a pattern of antiviral nucleic acid immune recognition that takes advantage of the inherent constraints on viral genome size.
History
DepositionDec 16, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 12, 2025Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Interferon-induced protein with tetratricopeptide repeats 2
B: Interferon-induced protein with tetratricopeptide repeats 3


Theoretical massNumber of molelcules
Total (without water)96,4422
Polymers96,4422
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: Protein Interferon-induced protein with tetratricopeptide repeats 2 / IFIT-2 / Glucocorticoid-attenuated response gene 39 protein / GARG-39 / Interferon-induced 54 kDa ...IFIT-2 / Glucocorticoid-attenuated response gene 39 protein / GARG-39 / Interferon-induced 54 kDa protein / IFI-54K / P54


Mass: 51702.301 Da / Num. of mol.: 1 / Fragment: residues 7-448 (Uniprot numbring)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Ifit2, Garg39, Ifi54, Isg54 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q64112
#2: Protein Interferon-induced protein with tetratricopeptide repeats 3 / IFIT-3 / Glucocorticoid-attenuated response gene 49 protein / GARG-49 / P49 / IRG2


Mass: 44740.059 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Ifit3, Garg49, Ifi49, Isg49 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q64345
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: Dimeric complex of Interferon-induced protein with tetratricopeptide repeats 2 and Interferon-induced protein with tetratricopeptide repeats 3
Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Molecular weightValue: 0.10222558 MDa / Experimental value: NO
Source (natural)Organism: Mus musculus (house mouse)
Source (recombinant)Organism: Escherichia coli BL21(DE3) (bacteria)
Buffer solutionpH: 7.5
Buffer component
IDConc.NameFormulaBuffer-ID
120 mMTris-HClNH2C(CH2OH)3HCl1
2150 mMSodium ChlorideNaCl1
31 mMDithiothreitolC4H10O2S21
SpecimenConc.: 3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil R1.2/1.3
VitrificationInstrument: HOMEMADE PLUNGER / Cryogen name: ETHANE-PROPANE / Humidity: 90 % / Chamber temperature: 277.15 K

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal magnification: 165000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 65 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 2355
Details: Images were collected on a Gatan K2 summit detector equipped with a Gatan BioContinuum energy filter
EM imaging opticsEnergyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV

-
Processing

EM software
IDNameVersionCategory
1cryoSPARCparticle selection
2EPU1image acquisition
4cryoSPARCCTF correction
9PHENIX1.21.1_5286model refinement
10cryoSPARCinitial Euler assignment
11cryoSPARCfinal Euler assignment
13cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 268606
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 3.22 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 80378 / Algorithm: FOURIER SPACE / Symmetry type: POINT
Atomic model buildingB value: 107.7 / Protocol: RIGID BODY FIT / Space: REAL
RefinementHighest resolution: 3.22 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0036873
ELECTRON MICROSCOPYf_angle_d0.5689234
ELECTRON MICROSCOPYf_dihedral_angle_d4.414910
ELECTRON MICROSCOPYf_chiral_restr0.04967
ELECTRON MICROSCOPYf_plane_restr0.0041205

+
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://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