The novel asymmetric entry intermediate of a picornavirus captured with nanodiscs

Sci Adv. 2016 Aug 24;2(8):e1501929. doi: 10.1126/sciadv.1501929. eCollection 2016 Aug.


Many nonenveloped viruses engage host receptors that initiate capsid conformational changes necessary for genome release. Structural studies on the mechanisms of picornavirus entry have relied on in vitro approaches of virus incubated at high temperatures or with excess receptor molecules to trigger the entry intermediate or A-particle. We have induced the coxsackievirus B3 entry intermediate by triggering the virus with full-length receptors embedded in lipid bilayer nanodiscs. These asymmetrically formed A-particles were reconstructed using cryo-electron microscopy and a direct electron detector. These first high-resolution structures of a picornavirus entry intermediate captured at a membrane with and without imposing icosahedral symmetry (3.9 and 7.8 Å, respectively) revealed a novel A-particle that is markedly different from the classical A-particles. The asymmetric receptor binding triggers minimal global capsid expansion but marked local conformational changes at the site of receptor interaction. In addition, viral proteins extrude from the capsid only at the site of extensive protein remodeling adjacent to the nanodisc. Thus, the binding of the receptor triggers formation of a unique site in preparation for genome release.

Keywords: A particle; CAR; CVB3; asymmetric; coxsackievirus; cryo; entry; nanodisc; structural biology; symmetry; virology; viruses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Capsid / chemistry
  • Capsid / ultrastructure
  • Capsid Proteins / chemistry
  • Capsid Proteins / genetics*
  • Capsid Proteins / ultrastructure
  • Coxsackievirus Infections / genetics
  • Coxsackievirus Infections / virology*
  • Cryoelectron Microscopy
  • Enterovirus / genetics*
  • Host-Pathogen Interactions / genetics*
  • Lipid Bilayers / chemistry
  • Lipid Bilayers / metabolism
  • Picornaviridae / chemistry
  • Picornaviridae / genetics
  • Picornaviridae / ultrastructure
  • Protein Binding
  • Protein Conformation
  • Virion / chemistry
  • Virion / ultrastructure
  • Virus Internalization


  • Capsid Proteins
  • Lipid Bilayers