[English] 日本語
![](img/lk-miru.gif)
- PDB-7jl0: Cryo-EM structure of MDA5-dsRNA in complex with TRIM65 PSpry doma... -
+
Open data
-
Basic information
Entry | Database: PDB / ID: 7jl0 | ||||||
---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of MDA5-dsRNA in complex with TRIM65 PSpry domain (Monomer) | ||||||
![]() |
| ||||||
![]() | HYDROLASE/IMMUNE SYSTEM/RNA / Innate immunity / Ubiquitin E3 ligase / dsRNA / RNA helicase / TRIM family / HYDROLASE-IMMUNE SYSTEM-RNA complex | ||||||
Function / homology | ![]() positive regulation of protein oligomerization / MDA-5 signaling pathway / regulation of type III interferon production / detection of virus / NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 / positive regulation of response to cytokine stimulus / pattern recognition receptor activity / TRAF6 mediated IRF7 activation / cytoplasmic pattern recognition receptor signaling pathway / negative regulation of viral genome replication ...positive regulation of protein oligomerization / MDA-5 signaling pathway / regulation of type III interferon production / detection of virus / NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 / positive regulation of response to cytokine stimulus / pattern recognition receptor activity / TRAF6 mediated IRF7 activation / cytoplasmic pattern recognition receptor signaling pathway / negative regulation of viral genome replication / type I interferon-mediated signaling pathway / cellular response to exogenous dsRNA / TRAF6 mediated NF-kB activation / protein K63-linked ubiquitination / antiviral innate immune response / protein sumoylation / positive regulation of interferon-alpha production / protein K48-linked ubiquitination / positive regulation of autophagy / ribonucleoprotein complex binding / positive regulation of interferon-beta production / Negative regulators of DDX58/IFIH1 signaling / RING-type E3 ubiquitin transferase / DDX58/IFIH1-mediated induction of interferon-alpha/beta / response to virus / Evasion by RSV of host interferon responses / cellular response to virus / negative regulation of inflammatory response / SARS-CoV-1 activates/modulates innate immune responses / positive regulation of interleukin-6 production / positive regulation of tumor necrosis factor production / ubiquitin protein ligase activity / double-stranded RNA binding / Ovarian tumor domain proteases / protein complex oligomerization / TRAF3-dependent IRF activation pathway / defense response to virus / RNA helicase activity / single-stranded RNA binding / Ub-specific processing proteases / RNA helicase / positive regulation of protein phosphorylation / innate immune response / SARS-CoV-2 activates/modulates innate and adaptive immune responses / ATP hydrolysis activity / mitochondrion / DNA binding / RNA binding / zinc ion binding / nucleoplasm / ATP binding / identical protein binding / nucleus / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.3 Å | ||||||
![]() | Kato, K. / Ahmad, S. / Hur, S. | ||||||
Funding support | ![]()
| ||||||
![]() | ![]() Title: Structural analysis of RIG-I-like receptors reveals ancient rules of engagement between diverse RNA helicases and TRIM ubiquitin ligases. Authors: Kazuki Kato / Sadeem Ahmad / Zixiang Zhu / Janet M Young / Xin Mu / Sehoon Park / Harmit S Malik / Sun Hur / ![]() ![]() Abstract: RNA helicases and E3 ubiquitin ligases mediate many critical functions in cells, but their actions have largely been studied in distinct biological contexts. Here, we uncover evolutionarily conserved ...RNA helicases and E3 ubiquitin ligases mediate many critical functions in cells, but their actions have largely been studied in distinct biological contexts. Here, we uncover evolutionarily conserved rules of engagement between RNA helicases and tripartite motif (TRIM) E3 ligases that lead to their functional coordination in vertebrate innate immunity. Using cryoelectron microscopy and biochemistry, we show that RIG-I-like receptors (RLRs), viral RNA receptors with helicase domains, interact with their cognate TRIM/TRIM-like E3 ligases through similar epitopes in the helicase domains. Their interactions are avidity driven, restricting the actions of TRIM/TRIM-like proteins and consequent immune activation to RLR multimers. Mass spectrometry and phylogeny-guided biochemical analyses further reveal that similar rules of engagement may apply to diverse RNA helicases and TRIM/TRIM-like proteins. Our analyses suggest not only conserved substrates for TRIM proteins but also, unexpectedly, deep evolutionary connections between TRIM proteins and RNA helicases, linking ubiquitin and RNA biology throughout animal evolution. | ||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 232.1 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 168.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 847 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 861.3 KB | Display | |
Data in XML | ![]() | 36.1 KB | Display | |
Data in CIF | ![]() | 54.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 22368MC ![]() 7jl1C ![]() 7jl2C ![]() 7jl3C ![]() 7jl4C M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
-RNA chain , 2 types, 2 molecules XY
#1: RNA chain | Mass: 4486.731 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
---|---|
#2: RNA chain | Mass: 4423.667 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
-Protein , 2 types, 2 molecules AB
#3: Protein | Mass: 84901.695 Da / Num. of mol.: 1 / Fragment: UNP residues 287-1025 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
---|---|
#4: Protein | Mass: 21643.365 Da / Num. of mol.: 1 / Fragment: TRIM65 PSpry domain (UNP residues 312-502) Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Non-polymers , 4 types, 4 molecules ![](data/chem/img/ZN.gif)
![](data/chem/img/ADP.gif)
![](data/chem/img/ALF.gif)
![](data/chem/img/MG.gif)
![](data/chem/img/ADP.gif)
![](data/chem/img/ALF.gif)
![](data/chem/img/MG.gif)
#5: Chemical | ChemComp-ZN / |
---|---|
#6: Chemical | ChemComp-ADP / |
#7: Chemical | ChemComp-ALF / |
#8: Chemical | ChemComp-MG / |
-Details
Has ligand of interest | N |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: Ternary complex of MDA5:dsRNA:TRIM65 / Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT |
---|---|
Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: unspecified |
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: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 76.5 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-
Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 49051 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 69.99 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
|