6EIT

Coxsackievirus A24v in complex with the D1-D2 fragment of ICAM-1


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.90 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Role of enhanced receptor engagement in the evolution of a pandemic acute hemorrhagic conjunctivitis virus.

Baggen, J.Hurdiss, D.L.Zocher, G.Mistry, N.Roberts, R.W.Slager, J.J.Guo, H.van Vliet, A.L.W.Wahedi, M.Benschop, K.Duizer, E.de Haan, C.A.M.de Vries, E.Casasnovas, J.M.de Groot, R.J.Arnberg, N.Stehle, T.Ranson, N.A.Thibaut, H.J.van Kuppeveld, F.J.M.

(2018) Proc Natl Acad Sci U S A 115: 397-402

  • DOI: https://doi.org/10.1073/pnas.1713284115
  • Primary Citation of Related Structures:  
    6EIT

  • PubMed 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, 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.


  • Organizational Affiliation

    Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584CL Utrecht, The Netherlands.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
VP1A [auth 1]305Coxsackievirus A24Mutation(s): 0 
UniProt
Find proteins for V9VEF3 (Coxsackievirus A24)
Explore V9VEF3 
Go to UniProtKB:  V9VEF3
Entity Groups  
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UniProt GroupV9VEF3
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
VP2B [auth 2]271Coxsackievirus A24Mutation(s): 0 
UniProt
Find proteins for V9VEF3 (Coxsackievirus A24)
Explore V9VEF3 
Go to UniProtKB:  V9VEF3
Entity Groups  
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UniProt GroupV9VEF3
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
VP3C [auth 3]240Coxsackievirus A24Mutation(s): 0 
UniProt
Find proteins for V9VEF3 (Coxsackievirus A24)
Explore V9VEF3 
Go to UniProtKB:  V9VEF3
Entity Groups  
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UniProt GroupV9VEF3
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
Intercellular adhesion molecule 1D [auth 4]85Homo sapiensMutation(s): 0 
Gene Names: ICAM1
UniProt & NIH Common Fund Data Resources
Find proteins for P05362 (Homo sapiens)
Explore P05362 
Go to UniProtKB:  P05362
PHAROS:  P05362
GTEx:  ENSG00000090339 
Entity Groups  
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UniProt GroupP05362
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.90 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
RECONSTRUCTIONRELION2.0

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Netherlands Organization for Scientific ResearchNetherlandsNWO-VICI-91812628
German Research FoundationGermanySFB685
Wellcome TrustUnited Kingdom102572/B/13/Z

Revision History  (Full details and data files)

  • Version 1.0: 2018-01-10
    Type: Initial release
  • Version 1.1: 2018-01-17
    Changes: Database references