+Open data
-Basic information
Entry | Database: PDB / ID: 6eit | ||||||||||||
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Title | Coxsackievirus A24v in complex with the D1-D2 fragment of ICAM-1 | ||||||||||||
Components |
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Keywords | VIRUS / Enterovirus / Receptor / Complex / picornavirus | ||||||||||||
Function / homology | Function and homology information regulation of leukocyte mediated cytotoxicity / T cell extravasation / positive regulation of cellular extravasation / regulation of ruffle assembly / : / T cell antigen processing and presentation / T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell / membrane to membrane docking / adhesion of symbiont to host / RNA-protein covalent cross-linking ...regulation of leukocyte mediated cytotoxicity / T cell extravasation / positive regulation of cellular extravasation / regulation of ruffle assembly / : / T cell antigen processing and presentation / T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell / membrane to membrane docking / adhesion of symbiont to host / RNA-protein covalent cross-linking / : / : / establishment of endothelial barrier / heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules / cell adhesion mediated by integrin / leukocyte cell-cell adhesion / leukocyte migration / Interleukin-10 signaling / immunological synapse / Integrin cell surface interactions / negative regulation of endothelial cell apoptotic process / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / ribonucleoside triphosphate phosphatase activity / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / cellular response to leukemia inhibitory factor / cellular response to glucose stimulus / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / transmembrane signaling receptor activity / integrin binding / cellular response to amyloid-beta / symbiont-mediated suppression of host gene expression / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / Interferon gamma signaling / viral capsid / virus receptor activity / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / signaling receptor activity / Interleukin-4 and Interleukin-13 signaling / collagen-containing extracellular matrix / positive regulation of ERK1 and ERK2 cascade / RNA helicase activity / receptor-mediated virion attachment to host cell / symbiont-mediated suppression of host innate immune response / cell adhesion / symbiont entry into host cell / membrane raft / induction by virus of host autophagy / external side of plasma membrane / cysteine-type endopeptidase activity / RNA-directed RNA polymerase / focal adhesion / viral RNA genome replication / virus-mediated perturbation of host defense response / RNA-dependent RNA polymerase activity / DNA-templated transcription / host cell nucleus / virion attachment to host cell / structural molecule activity / cell surface / proteolysis / RNA binding / extracellular space / extracellular exosome / ATP binding / membrane / metal ion binding / plasma membrane Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) Coxsackievirus A24 | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | ||||||||||||
Authors | Hurdiss, D.L. / Ranson, N.A. | ||||||||||||
Funding support | Netherlands, Germany, United Kingdom, 3items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2018 Title: Role of enhanced receptor engagement in the evolution of a pandemic acute hemorrhagic conjunctivitis virus. Authors: Jim Baggen / Daniel L Hurdiss / Georg Zocher / Nitesh Mistry / Richard W Roberts / Jasper J Slager / Hongbo Guo / Arno L W van Vliet / Maryam Wahedi / Kimberley Benschop / Erwin Duizer / ...Authors: Jim Baggen / Daniel L Hurdiss / Georg Zocher / Nitesh Mistry / Richard W Roberts / Jasper J Slager / Hongbo Guo / Arno L W van Vliet / Maryam Wahedi / Kimberley Benschop / Erwin Duizer / Cornelis A M de Haan / Erik de Vries / José M Casasnovas / Raoul J de Groot / Niklas Arnberg / Thilo Stehle / Neil A Ranson / Hendrik Jan Thibaut / Frank J M van Kuppeveld / Abstract: Acute hemorrhagic conjunctivitis (AHC) is a painful, contagious eye disease, with millions of cases in the last decades. Coxsackievirus A24 (CV-A24) was not originally associated with human disease, ...Acute hemorrhagic conjunctivitis (AHC) is a painful, contagious eye disease, with millions of cases in the last decades. Coxsackievirus A24 (CV-A24) was not originally associated with human disease, but in 1970 a pathogenic "variant" (CV-A24v) emerged, which is now the main cause of AHC. Initially, this variant circulated only in Southeast Asia, but it later spread worldwide, accounting for numerous AHC outbreaks and two pandemics. While both CV-A24 variant and nonvariant strains still circulate in humans, only variant strains cause AHC for reasons that are yet unknown. Since receptors are important determinants of viral tropism, we set out to map the CV-A24 receptor repertoire and establish whether changes in receptor preference have led to the increased pathogenicity and rapid spread of CV-A24v. Here, we identify ICAM-1 as an essential receptor for both AHC-causing and non-AHC strains. We provide a high-resolution cryo-EM structure of a virus-ICAM-1 complex, which revealed critical ICAM-1-binding residues. These data could help identify a possible conserved mode of receptor engagement among ICAM-1-binding enteroviruses and rhinoviruses. Moreover, we identify a single capsid substitution that has been adopted by all pandemic CV-A24v strains and we reveal that this adaptation enhances the capacity of CV-A24v to bind sialic acid. Our data elucidate the CV-A24v receptor repertoire and point to a role of enhanced receptor engagement in the adaptation to the eye, possibly enabling pandemic spread. | ||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6eit.cif.gz | 157.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6eit.ent.gz | 128.5 KB | Display | PDB format |
PDBx/mmJSON format | 6eit.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6eit_validation.pdf.gz | 833.2 KB | Display | wwPDB validaton report |
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Full document | 6eit_full_validation.pdf.gz | 838.3 KB | Display | |
Data in XML | 6eit_validation.xml.gz | 35.7 KB | Display | |
Data in CIF | 6eit_validation.cif.gz | 54.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ei/6eit ftp://data.pdbj.org/pub/pdb/validation_reports/ei/6eit | HTTPS FTP |
-Related structure data
Related structure data | 3880MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Symmetry | Point symmetry: (Schoenflies symbol: I (icosahedral)) |
-Components
#1: Protein | Mass: 34378.371 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Coxsackievirus A24 / Cell line: Normal human conjunctival (NHC) cells / References: UniProt: G3C8J7, UniProt: V9VEF3*PLUS |
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#2: Protein | Mass: 29817.412 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Coxsackievirus A24 / Cell line: Normal human conjunctival (NHC) cells / References: UniProt: A0A088F913, UniProt: V9VEF3*PLUS |
#3: Protein | Mass: 26637.746 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Coxsackievirus A24 / Cell line: Normal human conjunctival (NHC) cells / References: UniProt: Q0GYP7, UniProt: V9VEF3*PLUS |
#4: Protein | Mass: 9297.600 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ICAM1 / Cell line (production host): CHO Lec3.2.8.1 cells / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: P05362 |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component |
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Molecular weight | Value: 8 MDa / Experimental value: NO | ||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) | Organism: Cricetulus griseus (Chinese hamster) | ||||||||||||||||||||||||
Details of virus | Empty: NO / Enveloped: NO / Isolate: STRAIN / Type: VIRION | ||||||||||||||||||||||||
Natural host | Organism: Homo sapiens | ||||||||||||||||||||||||
Virus shell | Diameter: 300 nm / Triangulation number (T number): 3 | ||||||||||||||||||||||||
Buffer solution | pH: 7.5 Details: TBS buffer (Coxsackievirus A24v) Phosphate buffer (ICAM-1 D1-D2) | ||||||||||||||||||||||||
Specimen | Conc.: 10 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 400 divisions/in. Grid type: Lacey grids coated in a 3 nm carbon film (Agar Scientific, UK) | ||||||||||||||||||||||||
Vitrification | Instrument: LEICA EM GP / Cryogen name: ETHANE / Humidity: 80 % / Chamber temperature: 8 K Details: On-grid binding of the receptor was performed by applying 3 microliters of ICAM-1 (9.85 mg/ml) to the pre-blotted, virus-containing grid, and leaving for 30 seconds before blotting and freezing |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 1.5 sec. / Electron dose: 60 e/Å2 / Detector mode: INTEGRATING / Film or detector model: FEI FALCON III (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 2652 |
-Processing
EM software | Name: RELION / Version: 2 / Category: 3D reconstruction |
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CTF correction | Details: gCTF / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
Symmetry | Point symmetry: I (icosahedral) |
3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 26311 / Symmetry type: POINT |
Atomic model building | Protocol: OTHER / Space: REAL |