[English] 日本語
Yorodumi
- PDB-9h1z: Cryo-EM Structure of human OAS2 Dimer -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9h1z
TitleCryo-EM Structure of human OAS2 Dimer
Components2'-5'-oligoadenylate synthase 2
KeywordsRNA BINDING PROTEIN / nucleotidyltransferase / zinc / oligoadenylate synthetase / innate immunity
Function / homology
Function and homology information


regulation of lactation / 2'-5' oligoadenylate synthase / 2'-5'-oligoadenylate synthetase activity / interleukin-27-mediated signaling pathway / OAS antiviral response / RNA catabolic process / nucleobase-containing compound metabolic process / type I interferon-mediated signaling pathway / negative regulation of viral genome replication / RSV-host interactions ...regulation of lactation / 2'-5' oligoadenylate synthase / 2'-5'-oligoadenylate synthetase activity / interleukin-27-mediated signaling pathway / OAS antiviral response / RNA catabolic process / nucleobase-containing compound metabolic process / type I interferon-mediated signaling pathway / negative regulation of viral genome replication / RSV-host interactions / antiviral innate immune response / positive regulation of interferon-beta production / response to virus / Interferon gamma signaling / positive regulation of tumor necrosis factor production / Interferon alpha/beta signaling / double-stranded RNA binding / defense response to virus / defense response to bacterium / intracellular membrane-bounded organelle / perinuclear region of cytoplasm / nucleoplasm / ATP binding / metal ion binding / membrane / cytosol / cytoplasm
Similarity search - Function
2-5-oligoadenylate synthetase, N-terminal conserved site / 2'-5'-oligoadenylate synthases signature 1. / 2-5-oligoadenylate synthetase, C-terminal conserved site / 2'-5'-oligoadenylate synthetase 1, domain 2/C-terminal / 2'-5'-oligoadenylate synthetase 1, domain 2, C-terminus / 2'-5'-oligoadenylate synthases signature 2. / 2'-5'-oligoadenylate synthase N-terminal region profile. / 2-5OAS/ClassI-CCAase, nucleotidyltransferase domain / Polymerase, nucleotidyl transferase domain / Nucleotidyltransferase domain / Nucleotidyltransferase superfamily
Similarity search - Domain/homology
2'-5'-oligoadenylate synthase 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsMerold, V.R. / Lammens, K. / de Oliveira Mann, C.C.
Funding support Germany, European Union, 3items
OrganizationGrant numberCountry
German Research Foundation (DFG)369799452 Germany
German Research Foundation (DFG)458004906 Germany
European Research Council (ERC)101117085European Union
CitationJournal: Mol Cell / Year: 2025
Title: Structural basis for OAS2 regulation and its antiviral function.
Authors: Veronika Merold / Indra Bekere / Stefanie Kretschmer / Adrian F Schnell / Dorota Kmiec / Rinu Sivarajan / Katja Lammens / Rou Liu / Julia Mergner / Julia Teppert / Maximilian Hirschenberger ...Authors: Veronika Merold / Indra Bekere / Stefanie Kretschmer / Adrian F Schnell / Dorota Kmiec / Rinu Sivarajan / Katja Lammens / Rou Liu / Julia Mergner / Julia Teppert / Maximilian Hirschenberger / Alexander Henrici / Sarah Hammes / Kathrin Buder / Marcus Weitz / Karl Hackmann / Lars M Koenig / Andreas Pichlmair / Nadine Schwierz / Konstantin M J Sparrer / Min Ae Lee-Kirsch / Carina C de Oliveira Mann /
Abstract: Oligoadenylate synthetase (OAS) proteins are immune sensors for double-stranded RNA and are critical for restricting viruses. OAS2 comprises two OAS domains, only one of which can synthesize 2'-5'- ...Oligoadenylate synthetase (OAS) proteins are immune sensors for double-stranded RNA and are critical for restricting viruses. OAS2 comprises two OAS domains, only one of which can synthesize 2'-5'-oligoadenylates for RNase L activation. Existing structures of OAS1 provide a model for enzyme activation, but they do not explain how multiple OAS domains discriminate RNA length. Here, we discover that human OAS2 exists in an auto-inhibited state as a zinc-mediated dimer and present a mechanism for RNA length discrimination: the catalytically deficient domain acts as a molecular ruler that prevents autoreactivity to short RNAs. We demonstrate that dimerization and myristoylation localize OAS2 to Golgi membranes and that this is required for OAS2 activation and the restriction of viruses that exploit the endomembrane system for replication, e.g., coronaviruses. Finally, our results highlight the non-redundant role of OAS proteins and emphasize the clinical relevance of OAS2 by identifying a patient with a loss-of-function mutation associated with autoimmune disease.
History
DepositionOct 10, 2024Deposition site: PDBE / Processing site: PDBE
Revision 1.0May 28, 2025Provider: repository / Type: Initial release
Revision 1.1Jun 4, 2025Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.pdbx_database_id_PubMed / _citation.title / _em_admin.last_update
Revision 1.2Jun 18, 2025Group: Data collection / Database references / Category: citation / em_admin
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: 2'-5'-oligoadenylate synthase 2
B: 2'-5'-oligoadenylate synthase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)169,5673
Polymers169,5022
Non-polymers651
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable, gel filtration, native gel electrophoresis
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

#1: Protein 2'-5'-oligoadenylate synthase 2 / (2-5')oligo(A) synthase 2 / 2-5A synthase 2 / p69 OAS / p71 OAS / p69OAS / p71OAS


Mass: 84750.930 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: OAS2 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P29728, 2'-5' oligoadenylate synthase
#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: OAS2 dimer with zinc / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Molecular weightValue: 0.163 MDa / Experimental value: YES
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Trichoplusia ni (cabbage looper)
Buffer solutionpH: 7.5
Buffer component
IDConc.NameFormulaBuffer-ID
185 mMNaClNaCl1
225 mMHEPES, pH7.5HEPES1
SpecimenConc.: 0.6 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: COPPER / Grid type: Quantifoil R2/1
VitrificationInstrument: LEICA PLUNGER / Cryogen name: ETHANE-PROPANE / Humidity: 95 % / Chamber temperature: 288.15 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 defocus max: 2900 nm / Nominal defocus min: 1400 nm
Specimen holderCryogen: NITROGEN
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

-
Processing

EM softwareName: cryoSPARC / Category: particle selection
CTF correctionType: PHASE FLIPPING ONLY
3D reconstructionResolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 532195 / Symmetry type: POINT

+
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