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Yorodumi- EMDB-22368: Cryo-EM structure of MDA5-dsRNA in complex with TRIM65 PSpry doma... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-22368 | |||||||||
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Title | Cryo-EM structure of MDA5-dsRNA in complex with TRIM65 PSpry domain (Monomer) | |||||||||
Map data | The map was postprocessed in Relion | |||||||||
Sample |
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Keywords | Innate immunity / Ubiquitin E3 ligase / dsRNA / RNA helicase / TRIM family / HYDROLASE-IMMUNE SYSTEM-RNA complex | |||||||||
Function / homology | Function and homology information 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 / negative regulation of viral genome replication / type I interferon-mediated signaling pathway ...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 / negative regulation of viral genome replication / type I interferon-mediated signaling pathway / cellular response to exogenous dsRNA / cytoplasmic pattern recognition receptor signaling pathway / protein K63-linked ubiquitination / positive regulation of interferon-alpha production / antiviral innate immune response / TRAF6 mediated NF-kB activation / protein sumoylation / protein K48-linked ubiquitination / positive regulation of autophagy / ribonucleoprotein complex binding / positive regulation of interferon-beta production / Negative regulators of DDX58/IFIH1 signaling / response to virus / RING-type E3 ubiquitin transferase / DDX58/IFIH1-mediated induction of interferon-alpha/beta / cellular response to virus / negative regulation of inflammatory response / positive regulation of interleukin-6 production / ubiquitin protein ligase activity / SARS-CoV-1 activates/modulates innate immune responses / Ovarian tumor domain proteases / positive regulation of tumor necrosis factor production / double-stranded RNA binding / 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 / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.3 Å | |||||||||
Authors | Kato K / Ahmad S | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Mol Cell / Year: 2021 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 |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_22368.map.gz | 4.3 MB | EMDB map data format | |
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Header (meta data) | emd-22368-v30.xml emd-22368.xml | 14.6 KB 14.6 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_22368_fsc.xml | 9.2 KB | Display | FSC data file |
Images | emd_22368.png | 23.9 KB | ||
Filedesc metadata | emd-22368.cif.gz | 6.3 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-22368 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22368 | HTTPS FTP |
-Related structure data
Related structure data | 7jl0MC 7jl1C 7jl2C 7jl3C 7jl4C C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_22368.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | The map was postprocessed in Relion | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.03594 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Ternary complex of MDA5:dsRNA:TRIM65
Entire | Name: Ternary complex of MDA5:dsRNA:TRIM65 |
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Components |
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-Supramolecule #1: Ternary complex of MDA5:dsRNA:TRIM65
Supramolecule | Name: Ternary complex of MDA5:dsRNA:TRIM65 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: RNA (5'-R(P*GP*AP*CP*UP*GP*AP*CP*UP*GP*AP*CP*UP*GP*A)-3')
Macromolecule | Name: RNA (5'-R(P*GP*AP*CP*UP*GP*AP*CP*UP*GP*AP*CP*UP*GP*A)-3') type: rna / ID: 1 / Number of copies: 1 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 4.486731 KDa |
Sequence | String: GACUGACUGA CUGA |
-Macromolecule #2: RNA (5'-R(P*UP*CP*AP*GP*UP*CP*AP*GP*UP*CP*AP*GP*UP*C)-3')
Macromolecule | Name: RNA (5'-R(P*UP*CP*AP*GP*UP*CP*AP*GP*UP*CP*AP*GP*UP*C)-3') type: rna / ID: 2 / Number of copies: 1 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 4.423667 KDa |
Sequence | String: UCAGUCAGUC AGUC |
-Macromolecule #3: Interferon-induced helicase C domain-containing protein 1
Macromolecule | Name: Interferon-induced helicase C domain-containing protein 1 type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO / EC number: RNA helicase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 84.901695 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MGSDSDEENV AARASPEPEL QLRPYQMEVA QPALEGKNII ICLPTGSGKT RVAVYIAKDH LDKKKKASEP GKVIVLVNKV LLVEQLFRK EFQPFLKKWY RVIGLSGDTQ LKISFPEVVK SCDIIISTAQ ILENSLLNLE NGEDAGVQLS DFSLIIIDEC H HTNKEAVY ...String: MGSDSDEENV AARASPEPEL QLRPYQMEVA QPALEGKNII ICLPTGSGKT RVAVYIAKDH LDKKKKASEP GKVIVLVNKV LLVEQLFRK EFQPFLKKWY RVIGLSGDTQ LKISFPEVVK SCDIIISTAQ ILENSLLNLE NGEDAGVQLS DFSLIIIDEC H HTNKEAVY NNIMRHYLMQ KLKNNRLKKE NKPVIPLPQI LGLTASPGVG GATKQAKAEE HILKLCANLD AFTIKTVKEN LD QLKNQIQ EPCKKFAIAD ATREDPFKEK LLEIMTRIQT YCQMSPMSDF GTQPYEQWAI QMEKKAAKEG NRKERVCAEH LRK YNEALQ INDTIRMIDA YTHLETFYNE EKDKKFAVIE DDSDEGGDDE YCDGDEDEDD LKKPLKLDET DRFLMTLFFE NNKM LKRLA ENPEYENEKL TKLRNTIMEQ YTRTEESARG IIFTKTRQSA YALSQWITEN EKFAEVGVKA HHLIGAGHSS EFKPM TQNE QKEVISKFRT GKINLLIATT VAEEGLDIKE CNIVIRYGLV TNEIAMVQAR GRARADESTY VLVAHSGSGV IERETV NDF REKMMYKAIH CVQNMKPEEY AHKILELQMQ SIMEKKMKTK RNIAKHYKNN PSLITFLCKN CSVLACSGED IHVIEKM HH VNMTPEFKEL YIVREKKTLQ KKCADYQING EIICKCGQAW GTMMVHKGLD LPCLKIRNFV VVFKNNSTKK QYKKWVEL P ITFPNLDYSE CCLFSDED UniProtKB: Interferon-induced helicase C domain-containing protein 1 |
-Macromolecule #4: Tripartite motif-containing protein 65
Macromolecule | Name: Tripartite motif-containing protein 65 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 21.643365 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: LAPVPSTVCP LRRKLWQNYR NLTFDPVSAN RHFYLSRQDQ QVKHLRQSRG PGGPGSFELW QVQCAQSFQA GHHYWEVRAS DHSVTLGVS YPQLPRSRLG PHTDNIGRGP SSWGLCVQED SLQAWHNGEA QRLPGVSGRL LGMDLDLASG CLTFYSLEPQ T QPLYTFHA LFNQPLTPVF WLLEGRTLTL CHQ UniProtKB: E3 ubiquitin-protein ligase TRIM65 |
-Macromolecule #5: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 5 / Number of copies: 1 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Macromolecule #6: ADENOSINE-5'-DIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-DIPHOSPHATE / type: ligand / ID: 6 / Number of copies: 1 / Formula: ADP |
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Molecular weight | Theoretical: 427.201 Da |
Chemical component information | ChemComp-ADP: |
-Macromolecule #7: TETRAFLUOROALUMINATE ION
Macromolecule | Name: TETRAFLUOROALUMINATE ION / type: ligand / ID: 7 / Number of copies: 1 / Formula: ALF |
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Molecular weight | Theoretical: 102.975 Da |
Chemical component information | ChemComp-ALF: |
-Macromolecule #8: MAGNESIUM ION
Macromolecule | Name: MAGNESIUM ION / type: ligand / ID: 8 / Number of copies: 1 / Formula: MG |
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Molecular weight | Theoretical: 24.305 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 7.5 |
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Grid | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 76.5 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |