|Entry||Database: PDB / ID: 6eit|
|Title||Coxsackievirus A24v in complex with the D1-D2 fragment of ICAM-1|
|Keywords||VIRUS / Enterovirus / Receptor / Complex / picornavirus|
|Function/homology||positive regulation of cellular extravasation / regulation of leukocyte mediated cytotoxicity / response to sulfur dioxide / T cell antigen processing and presentation / response to gonadotropin / establishment of Sertoli cell barrier / Intercellular adhesion molecule / Intercellular adhesion molecule, N-terminal / Intercellular adhesion molecule (ICAM), N-terminal domain / Intercellular adhesion molecule/vascular cell adhesion molecule, N-terminal ...positive regulation of cellular extravasation / regulation of leukocyte mediated cytotoxicity / response to sulfur dioxide / T cell antigen processing and presentation / response to gonadotropin / establishment of Sertoli cell barrier / Intercellular adhesion molecule / Intercellular adhesion molecule, N-terminal / Intercellular adhesion molecule (ICAM), N-terminal domain / Intercellular adhesion molecule/vascular cell adhesion molecule, N-terminal / regulation of ruffle assembly / membrane to membrane docking / T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell / establishment of endothelial intestinal barrier / positive regulation of leukocyte adhesion to vascular endothelial cell / acute inflammatory response to antigenic stimulus / adhesion of symbiont to host / cellular response to nutrient levels / establishment of endothelial barrier / cellular response to interleukin-6 / cell adhesion mediated by integrin / receptor-mediated virion attachment to host cell / response to ionizing radiation / cellular response to alkaloid / leukocyte cell-cell adhesion / heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules / immunological synapse / response to copper ion / response to amphetamine / positive regulation of actin filament polymerization / Interleukin-10 signaling / T=pseudo3 icosahedral viral capsid / Poliovirus 3A protein-like / Peptidase C3, picornavirus core protein 2A / Poliovirus 3A protein like / Poliovirus core protein 3a, soluble domain / Picornavirus 2B protein / Picornavirus coat protein VP4 / picornain 2A / Picornavirus 2B protein / Picornavirus core protein 2A / pore-mediated entry of viral genome into host cell / suppression by virus of host mRNA export from nucleus / negative regulation of calcium ion transport / positive regulation of vasoconstriction / cellular response to interleukin-1 / suppression by virus of host RIG-I activity / picornain 3C / endocytosis involved in viral entry into host cell / response to insulin / negative regulation of endothelial cell apoptotic process / ovarian follicle development / cellular response to leukemia inhibitory factor / RNA-protein covalent cross-linking / host cell cytoplasmic vesicle membrane / Peptidase C3A/C3B, picornaviral / Picornavirus coat protein (VP4) / Integrin cell surface interactions / cell aging / cellular response to glucose stimulus / cellular response to dexamethasone stimulus / Picornavirus capsid / Superfamily 3 helicase of positive ssRNA viruses domain profile. / Helicase, superfamily 3, single-stranded RNA virus / Helicase, superfamily 3, single-stranded DNA/RNA virus / RNA helicase / 3C cysteine protease (picornain 3C) / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / Picornavirus/Calicivirus coat protein / RNA-directed RNA polymerase, C-terminal domain / sensory perception of sound / response to amino acid / RNA dependent RNA polymerase / positive regulation of GTPase activity / transmembrane signaling receptor activity / RNA helicase activity / pore formation by virus in membrane of host cell / integral to membrane of host cell / virus receptor activity / viral capsid / nucleoside-triphosphatase / cellular response to tumor necrosis factor / Interferon gamma signaling / cellular response to hypoxia / picornavirus capsid protein / interferon-gamma-mediated signaling pathway / go:0004872: / integrin binding / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / extracellular matrix organization / RNA-directed RNA polymerase / induction by virus of host autophagy / ion channel activity / protein complex oligomerization / suppression by virus of host gene expression / regulation of immune response / RdRp of positive ssRNA viruses catalytic domain profile. / RNA-directed RNA polymerase, catalytic domain / positive regulation of peptidyl-tyrosine phosphorylation / extracellular matrix|
Function and homology information
|Specimen source||Homo sapiens / human / |
Coxsackievirus A24 / virus
|Method||Electron microscopy (3.9 Å resolution / Particle / Single particle) / Transmission electron microscopy|
|Authors||Hurdiss, D.L. / Ranson, N.A.|
|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 / 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.
SummaryFull reportAbout validation report
|Date||Deposition: Sep 19, 2017 / Release: Jan 10, 2018|
Downloads & links
4: Intercellular adhesion molecule 1
1: VP1x 60
4: Intercellular adhesion molecule 1
|#1: Protein/peptide|| |
Mass: 34378.371 Da / Num. of mol.: 1 / Source: (natural) Coxsackievirus A24 / virus / Cell line: Normal human conjunctival (NHC) cells / References: UniProt:G3C8J7, UniProt:V9VEF3*PLUS
|#2: Protein/peptide|| |
Mass: 29817.412 Da / Num. of mol.: 1 / Source: (natural) Coxsackievirus A24 / virus / Cell line: Normal human conjunctival (NHC) cells / References: UniProt:A0A088F913, UniProt:V9VEF3*PLUS
|#3: Protein/peptide|| |
Mass: 26637.746 Da / Num. of mol.: 1 / Source: (natural) Coxsackievirus A24 / virus / Cell line: Normal human conjunctival (NHC) cells / References: UniProt:Q0GYP7, UniProt:V9VEF3*PLUS
|#4: Protein/peptide|| |
Mass: 9297.600 Da / Num. of mol.: 1 / Source: (gene. exp.) Homo sapiens / human / / Gene: ICAM1 / Cell line (production host): CHO Lec188.8.131.52 cells / Production host: Cricetulus griseus / References: UniProt:P05362
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: PARTICLE / Reconstruction method: SINGLE PARTICLE|
|Molecular weight||Value: 8 deg. / Units: MEGADALTONS / Experimental value: NO|
|Source (recombinant)||Organism: Cricetulus griseus|
|Details of virus||Empty: NO / Enveloped: NO / Virus isolate: STRAIN / Virus type: VIRION|
|Natural host||Organism: Homo sapiens|
|Virus shell||Diameter: 300 Å / Triangulation number (T number): 3|
|Buffer solution||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|
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 kelvins|
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
Model: Titan Krios / Image courtesy: FEI Company
|Microscopy||Microscope 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) / Number of grids imaged: 1 / Number of real images: 2652|
|EM software||Name: RELION / Version: 2 / Category: RECONSTRUCTION|
|CTF correction||Details: gCTF / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION|
|Symmetry||Point symmetry: I|
|3D reconstruction||Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number of particles: 26311 / Symmetry type: POINT|
|Atomic model building||Ref protocol: OTHER / Ref space: REAL|
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