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- PDB-6diz: EV-A71 strain 11316 complexed with tryptophan dendrimer MADAL_0385 -
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Open data
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Basic information
Entry | Database: PDB / ID: 6diz | ||||||
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Title | EV-A71 strain 11316 complexed with tryptophan dendrimer MADAL_0385 | ||||||
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![]() | VIRUS / tryptophan dendrimers / EV-A71 / 5-fold vertex / Cryo-EM | ||||||
Function / homology | ![]() symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / symbiont-mediated suppression of host gene expression ...symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / symbiont-mediated suppression of host gene expression / viral capsid / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / RNA helicase activity / induction by virus of host autophagy / RNA-directed RNA polymerase / viral RNA genome replication / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / DNA-templated transcription / host cell nucleus / virion attachment to host cell / structural molecule activity / ATP hydrolysis activity / proteolysis / RNA binding / ATP binding / metal ion binding Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.59 Å | ||||||
![]() | Sun, L. / Lee, H. / Thibaut, H.J. / Rivero-Buceta, E. / Martinez-Gualda, B. / Delang, L. / Leyssen, P. / Gago, F. / San-Felix, A. / Hafenstein, S. ...Sun, L. / Lee, H. / Thibaut, H.J. / Rivero-Buceta, E. / Martinez-Gualda, B. / Delang, L. / Leyssen, P. / Gago, F. / San-Felix, A. / Hafenstein, S. / Mirabelli, C. / Neyts, J. | ||||||
Funding support | 1items
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![]() | ![]() Title: Viral engagement with host receptors blocked by a novel class of tryptophan dendrimers that targets the 5-fold-axis of the enterovirus-A71 capsid. Authors: Liang Sun / Hyunwook Lee / Hendrik Jan Thibaut / Kristina Lanko / Eva Rivero-Buceta / Carol Bator / Belen Martinez-Gualda / Kai Dallmeier / Leen Delang / Pieter Leyssen / Federico Gago / Ana ...Authors: Liang Sun / Hyunwook Lee / Hendrik Jan Thibaut / Kristina Lanko / Eva Rivero-Buceta / Carol Bator / Belen Martinez-Gualda / Kai Dallmeier / Leen Delang / Pieter Leyssen / Federico Gago / Ana San-Félix / Susan Hafenstein / Carmen Mirabelli / Johan Neyts / ![]() ![]() ![]() Abstract: Enterovirus A71 (EV-A71) is a non-polio neurotropic enterovirus with pandemic potential. There are no antiviral agents approved to prevent or treat EV-A71 infections. We here report on the molecular ...Enterovirus A71 (EV-A71) is a non-polio neurotropic enterovirus with pandemic potential. There are no antiviral agents approved to prevent or treat EV-A71 infections. We here report on the molecular mechanism by which a novel class of tryptophan dendrimers inhibits (at low nanomolar to high picomolar concentration) EV-A71 replication in vitro. A lead compound in the series (MADAL385) prevents binding and internalization of the virus but does not, unlike classical capsid binders, stabilize the particle. By means of resistance selection, reverse genetics and cryo-EM, we map the binding region of MADAL385 to the 5-fold vertex of the viral capsid and demonstrate that a single molecule binds to each vertex. By interacting with this region, MADAL385 prevents the interaction of the virus with its cellular receptors PSGL1 and heparan sulfate, thereby blocking the attachment of EV-A71 to the host cells. | ||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 156.7 KB | Display | ![]() |
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PDB format | ![]() | 122.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 7913MC ![]() 7905C C: citing same article ( M: map data used to model this data |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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1 | ![]()
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3 | ![]()
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Symmetry | Point symmetry: (Schoenflies symbol: I (icosahedral)) |
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Components
#1: Protein | Mass: 32748.754 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#2: Protein | Mass: 26946.342 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#3: Protein | Mass: 26540.332 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#4: Protein | Mass: 8367.070 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
#5: Chemical | ChemComp-SPH / |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Enterovirus A71 / Type: VIRUS / Entity ID: #1-#4 / Source: NATURAL |
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Source (natural) | Organism: ![]() ![]() |
Details of virus | Empty: NO / Enveloped: NO / Isolate: STRAIN / Type: VIRION |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 44 e/Å2 / Film or detector model: FEI FALCON III (4k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.59 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 11813 / Symmetry type: POINT |