[English] 日本語
Yorodumi
- PDB-8ik3: Structure of Stimulator of interferon genes/ligand complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8ik3
TitleStructure of Stimulator of interferon genes/ligand complex
ComponentsStimulator of interferon genes protein,Immune protein Tsi3
KeywordsIMMUNE SYSTEM / complex
Function / homology
Function and homology information


STING complex / STAT6-mediated induction of chemokines / protein localization to endoplasmic reticulum / 2',3'-cyclic GMP-AMP binding / cyclic-di-GMP binding / STING mediated induction of host immune responses / serine/threonine protein kinase complex / positive regulation of type I interferon-mediated signaling pathway / IRF3-mediated induction of type I IFN / proton channel activity ...STING complex / STAT6-mediated induction of chemokines / protein localization to endoplasmic reticulum / 2',3'-cyclic GMP-AMP binding / cyclic-di-GMP binding / STING mediated induction of host immune responses / serine/threonine protein kinase complex / positive regulation of type I interferon-mediated signaling pathway / IRF3-mediated induction of type I IFN / proton channel activity / cGAS/STING signaling pathway / reticulophagy / pattern recognition receptor signaling pathway / cytoplasmic pattern recognition receptor signaling pathway / cellular response to exogenous dsRNA / protein complex oligomerization / positive regulation of macroautophagy / autophagosome membrane / autophagosome assembly / positive regulation of type I interferon production / cellular response to interferon-beta / signaling adaptor activity / positive regulation of defense response to virus by host / antiviral innate immune response / endoplasmic reticulum-Golgi intermediate compartment membrane / activation of innate immune response / cytoplasmic vesicle membrane / Regulation of innate immune responses to cytosolic DNA / autophagosome / positive regulation of interferon-beta production / positive regulation of DNA-binding transcription factor activity / secretory granule membrane / SARS-CoV-1 activates/modulates innate immune responses / positive regulation of protein binding / peroxisome / regulation of inflammatory response / defense response to virus / RNA polymerase II-specific DNA-binding transcription factor binding / mitochondrial outer membrane / endosome / ciliary basal body / cilium / Golgi membrane / innate immune response / ubiquitin protein ligase binding / Neutrophil degranulation / endoplasmic reticulum membrane / protein kinase binding / perinuclear region of cytoplasm / SARS-CoV-2 activates/modulates innate and adaptive immune responses / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / nucleoplasm / metal ion binding / identical protein binding / plasma membrane / cytosol
Similarity search - Function
: / : / Type six secretion immunity 3 domain / : / STING transmembrane domain / : / : / Stimulator of interferon genes protein / Stimulator of interferon genes protein, C-terminal domain superfamily / STING ligand-binding domain / Prokaryotic membrane lipoprotein lipid attachment site profile.
Similarity search - Domain/homology
cGAMP / Stimulator of interferon genes protein / Immune protein Tsi3
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsLu, D.F. / Shang, G.J.
Funding support China, 1items
OrganizationGrant numberCountry
Ministry of Science and Technology (MoST, China)2021YFC2301400 China
CitationJournal: Mol Cell / Year: 2023
Title: The mechanism of STING autoinhibition and activation.
Authors: Sheng Liu / Bo Yang / Yingxiang Hou / Kaige Cui / Xiaozhu Yang / Xiaoxiong Li / Lianwan Chen / Shichao Liu / Zhichao Zhang / Yuanyuan Jia / Yufeng Xie / Ying Xue / Xiaomei Li / Bingxue Yan / ...Authors: Sheng Liu / Bo Yang / Yingxiang Hou / Kaige Cui / Xiaozhu Yang / Xiaoxiong Li / Lianwan Chen / Shichao Liu / Zhichao Zhang / Yuanyuan Jia / Yufeng Xie / Ying Xue / Xiaomei Li / Bingxue Yan / Changxin Wu / Wen Deng / Jianxun Qi / Defen Lu / George F Gao / Peiyi Wang / Guijun Shang /
Abstract: 2',3'-cGAMP, produced by the DNA sensor cGAS, activates stimulator of interferon genes (STING) and triggers immune response during infection. Tremendous effort has been placed on unraveling the ...2',3'-cGAMP, produced by the DNA sensor cGAS, activates stimulator of interferon genes (STING) and triggers immune response during infection. Tremendous effort has been placed on unraveling the mechanism of STING activation. However, little is known about STING inhibition. Here, we found that apo-STING exhibits a bilayer with head-to-head as well as side-by-side packing, mediated by its ligand-binding domain (LBD). This type of assembly holds two endoplasmic reticulum (ER) membranes together not only to prevent STING ER exit but also to eliminate the recruitment of TBK1, representing the autoinhibited state of STING. Additionally, we obtained the filament structure of the STING/2',3'-cGAMP complex, which adopts a bent monolayer assembly mediated by LBD and transmembrane domain (TMD). The active, curved STING polymer could deform ER membrane to support its ER exit and anterograde transportation. Our data together provide a panoramic vision regarding STING autoinhibition and activation, which adds substantially to current understanding of the cGAS-STING pathway.
History
DepositionFeb 28, 2023Deposition site: PDBJ / Processing site: PDBC
Revision 1.0May 17, 2023Provider: repository / Type: Initial release
Revision 1.1May 1, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / citation
Item: _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Stimulator of interferon genes protein,Immune protein Tsi3
B: Stimulator of interferon genes protein,Immune protein Tsi3
C: Stimulator of interferon genes protein,Immune protein Tsi3
D: Stimulator of interferon genes protein,Immune protein Tsi3
E: Stimulator of interferon genes protein,Immune protein Tsi3
G: Stimulator of interferon genes protein,Immune protein Tsi3
F: Stimulator of interferon genes protein,Immune protein Tsi3
H: Stimulator of interferon genes protein,Immune protein Tsi3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)467,92212
Polymers465,2248
Non-polymers2,6984
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: Protein
Stimulator of interferon genes protein,Immune protein Tsi3 / hSTING / Endoplasmic reticulum interferon stimulator / ERIS / Mediator of IRF3 activation / hMITA / ...hSTING / Endoplasmic reticulum interferon stimulator / ERIS / Mediator of IRF3 activation / hMITA / Transmembrane protein 173 / Anti-toxin protein Tsi3


Mass: 58152.996 Da / Num. of mol.: 8
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: STING1, ERIS, MITA, STING, TMEM173, tsi3, PA3485 / Production host: Homo sapiens (human) / References: UniProt: Q86WV6, UniProt: Q9HYC4
#2: Chemical
ChemComp-1SY / cGAMP / 2',3' cGAMP / c-GMP-AMP / c[G(2',5')pA(3',5')p]


Mass: 674.411 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C20H24N10O13P2 / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: complex of stimulator of interferon genes and ligand / Type: COMPLEX / Entity ID: #1 / Source: MULTIPLE SOURCES
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5 / Details: 20mM HEPES, 150 mM NaCl, 1mM DTT
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 / Nominal defocus max: 2200 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

SoftwareName: PHENIX / Version: 1.19.2_4158: / Classification: refinement
CTF correctionType: NONE
3D reconstructionResolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 216426 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00421431
ELECTRON MICROSCOPYf_angle_d0.58829179
ELECTRON MICROSCOPYf_dihedral_angle_d12.5592944
ELECTRON MICROSCOPYf_chiral_restr0.0393271
ELECTRON MICROSCOPYf_plane_restr0.0053683

+
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