Molecular mechanism of alpha2beta1 integrin interaction with human echovirus 1

EMBO J. 2010 Jan 6;29(1):196-208. doi: 10.1038/emboj.2009.326. Epub 2009 Nov 19.


Conformational activation increases the affinity of integrins to their ligands. On ligand binding, further changes in integrin conformation elicit cellular signalling. Unlike any of the natural ligands of alpha2beta1 integrin, human echovirus 1 (EV1) seemed to bind more avidly a 'closed' than an activated 'open' form of the alpha2I domain. Furthermore, a mutation E336A in the alpha2 subunit, which inactivated alpha2beta1 as a collagen receptor, enhanced alpha2beta1 binding to EV1. Thus, EV1 seems to recognize an inactive integrin, and not even the virus binding could trigger the conformational activation of alpha2beta1. This was supported by the fact that the integrin clustering by EV1 did not activate the p38 MAP kinase pathway, a signalling pathway that was shown to be dependent on E336-related conformational changes in alpha2beta1. Furthermore, the mutation E336A did neither prevent EV1 induced and alpha2beta1 mediated protein kinase C activation nor EV1 internalization. Thus, in its entry strategy EV1 seems to rely on the activation of signalling pathways that are dependent on alpha2beta1 clustering, but do not require the conformational regulation of the receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Binding Sites
  • CHO Cells
  • Cell Line
  • Chlorocebus aethiops
  • Cricetinae
  • Cricetulus
  • Enterovirus B, Human / pathogenicity*
  • Enterovirus B, Human / physiology*
  • Humans
  • In Vitro Techniques
  • Integrin alpha2beta1 / chemistry
  • Integrin alpha2beta1 / genetics
  • Integrin alpha2beta1 / metabolism*
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Protein Conformation
  • Protein Structure, Tertiary
  • Receptors, Virus / chemistry
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Integrin alpha2beta1
  • Receptors, Virus
  • Recombinant Proteins
  • p38 Mitogen-Activated Protein Kinases