+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-38156 | |||||||||
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Title | Structure of enterovirus protease in complex host factor | |||||||||
Map data | ||||||||||
Sample |
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Keywords | host protein / VIRAL PROTEIN / CELL INVASION / CELL CYCLE | |||||||||
Function / homology | Function and homology information peptidyl-histidine methylation / regulation of uterine smooth muscle contraction / protein-histidine N-methyltransferase / protein-L-histidine N-tele-methyltransferase activity / actin modification / histone H3K36 methyltransferase activity / histone H3K4 methyltransferase activity / positive regulation of muscle cell differentiation / viral process / PKMTs methylate histone lysines ...peptidyl-histidine methylation / regulation of uterine smooth muscle contraction / protein-histidine N-methyltransferase / protein-L-histidine N-tele-methyltransferase activity / actin modification / histone H3K36 methyltransferase activity / histone H3K4 methyltransferase activity / positive regulation of muscle cell differentiation / viral process / PKMTs methylate histone lysines / peptidase activity / actin binding / RNA polymerase II-specific DNA-binding transcription factor binding / host cell cytoplasm / transcription coactivator activity / chromatin / positive regulation of DNA-templated transcription / positive regulation of transcription by RNA polymerase II / proteolysis / nucleoplasm / metal ion binding / cytoplasm Similarity search - Function | |||||||||
Biological species | Enterovirus A71 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.14 Å | |||||||||
Authors | Gao X / Cui S | |||||||||
Funding support | 1 items
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Citation | Journal: Nat Commun / Year: 2024 Title: The EV71 2A protease occupies the central cleft of SETD3 and disrupts SETD3-actin interaction. Authors: Xiaopan Gao / Bei Wang / Kaixiang Zhu / Linyue Wang / Bo Qin / Kun Shang / Wei Ding / Jianwei Wang / Sheng Cui / Abstract: SETD3 is an essential host factor for the replication of a variety of enteroviruses that specifically interacts with viral protease 2A. However, the interaction between SETD3 and the 2A protease has ...SETD3 is an essential host factor for the replication of a variety of enteroviruses that specifically interacts with viral protease 2A. However, the interaction between SETD3 and the 2A protease has not been fully characterized. Here, we use X-ray crystallography and cryo-electron microscopy to determine the structures of SETD3 complexed with the 2A protease of EV71 to 3.5 Å and 3.1 Å resolution, respectively. We find that the 2A protease occupies the V-shaped central cleft of SETD3 through two discrete sites. The relative positions of the two proteins vary in the crystal and cryo-EM structures, showing dynamic binding. A biolayer interferometry assay shows that the EV71 2A protease outcompetes actin for SETD3 binding. We identify key 2A residues involved in SETD3 binding and demonstrate that 2A's ability to bind SETD3 correlates with EV71 production in cells. Coimmunoprecipitation experiments in EV71 infected and 2A expressing cells indicate that 2A interferes with the SETD3-actin complex, and the disruption of this complex reduces enterovirus replication. Together, these results reveal the molecular mechanism underlying the interplay between SETD3, actin, and viral 2A during virus replication. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_38156.map.gz | 32.1 MB | EMDB map data format | |
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Header (meta data) | emd-38156-v30.xml emd-38156.xml | 16.5 KB 16.5 KB | Display Display | EMDB header |
Images | emd_38156.png | 58.6 KB | ||
Filedesc metadata | emd-38156.cif.gz | 6 KB | ||
Others | emd_38156_half_map_1.map.gz emd_38156_half_map_2.map.gz | 59.5 MB 59.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-38156 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-38156 | HTTPS FTP |
-Validation report
Summary document | emd_38156_validation.pdf.gz | 944.7 KB | Display | EMDB validaton report |
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Full document | emd_38156_full_validation.pdf.gz | 944.3 KB | Display | |
Data in XML | emd_38156_validation.xml.gz | 12.2 KB | Display | |
Data in CIF | emd_38156_validation.cif.gz | 14.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-38156 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-38156 | HTTPS FTP |
-Related structure data
Related structure data | 8x8qMC 8x77C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_38156.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.82 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_38156_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_38156_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : enterovirus protease in complex host factor
Entire | Name: enterovirus protease in complex host factor |
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Components |
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-Supramolecule #1: enterovirus protease in complex host factor
Supramolecule | Name: enterovirus protease in complex host factor / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Enterovirus A71 |
-Macromolecule #1: Actin-histidine N-methyltransferase
Macromolecule | Name: Actin-histidine N-methyltransferase / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 67.342047 KDa |
Recombinant expression | Organism: Baculovirus expression vector pFastBac1-HM |
Sequence | String: MGKKSRVKTQ KSGTGATATV SPKEILNLTS ELLQKCSSPA PGPGKEWEEY VQIRTLVEKI RKKQKGLSVT FDGKREDYFP DLMKWASEN GASVEGFEMV NFKEEGFGLR ATRDIKAEEL FLWVPRKLLM TVESAKNSVL GPLYSQDRIL QAMGNIALAF H LLCERASP ...String: MGKKSRVKTQ KSGTGATATV SPKEILNLTS ELLQKCSSPA PGPGKEWEEY VQIRTLVEKI RKKQKGLSVT FDGKREDYFP DLMKWASEN GASVEGFEMV NFKEEGFGLR ATRDIKAEEL FLWVPRKLLM TVESAKNSVL GPLYSQDRIL QAMGNIALAF H LLCERASP NSFWQPYIQT LPSEYDTPLY FEEDEVRYLQ STQAIHDVFS QYKNTARQYA YFYKVIQTHP HANKLPLKDS FT YEDYRWA VSSVMTRQNQ IPTEDGSRVT LALIPLWDMC NHTNGLITTG YNLEDDRCEC VALQDFRAGE QIYIFYGTRS NAE FVIHSG FFFDNNSHDR VKIKLGVSKS DRLYAMKAEV LARAGIPTSS VFALHFTEPP ISAQLLAFLR VFCMTEEELK EHLL GDSAI DRIFTLGNSE FPVSWDNEVK LWTFLEDRAS LLLKTYKTTI EEDKSVLKNH DLSVRAKMAI KLRLGEKEIL EKAVK SAAV NREYYRQQME EKAPLPKYEE SNLGLLESSV GDSRLPLVLR NLEEEAGVQD ALNIREAISK AKATENGLVN GENSIP NGT RSENESLNQE SKRAVEDAKG SSSDSTAGVK E UniProtKB: Actin-histidine N-methyltransferase |
-Macromolecule #2: 2A protein (Fragment)
Macromolecule | Name: 2A protein (Fragment) / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Enterovirus A71 |
Molecular weight | Theoretical: 16.562418 KDa |
Recombinant expression | Organism: Baculovirus expression vector pFastBac1-HM |
Sequence | String: GKFGQQSGAI YVGNFRVVNR HLATHNDWAN LVWEDSSRDL LVSSTTAQGC DTIARCNCQT GVYYCNSRRK HYPVSFSKPS LIYVEASEY YPARYQSHLM LAQGHSEPGD AGGILRCQHG VVGIVSTGGN GLVGFADVRD LLWLDEEAME Q UniProtKB: 2A protein |
-Macromolecule #3: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 3 / Number of copies: 1 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Temperature | Min: 70.0 K / Max: 80.0 K |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 66.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Calibrated defocus max: 2.5 µm / Calibrated defocus min: 1.8 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.8 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |