Structural rearrangements in the membrane penetration protein of a non-enveloped virus

Nature. 2004 Aug 26;430(7003):1053-8. doi: 10.1038/nature02836.


Non-enveloped virus particles (those that lack a lipid-bilayer membrane) must breach the membrane of a target host cell to gain access to its cytoplasm. So far, the molecular mechanism of this membrane penetration step has resisted structural analysis. The spike protein VP4 is a principal component in the entry apparatus of rotavirus, a non-enveloped virus that causes gastroenteritis and kills 440,000 children each year. Trypsin cleavage of VP4 primes the virus for entry by triggering a rearrangement that rigidifies the VP4 spikes. We have determined the crystal structure, at 3.2 A resolution, of the main part of VP4 that projects from the virion. The crystal structure reveals a coiled-coil stabilized trimer. Comparison of this structure with the two-fold clustered VP4 spikes in a approximately 12 A resolution image reconstruction from electron cryomicroscopy of trypsin-primed virions shows that VP4 also undergoes a second rearrangement, in which the oligomer reorganizes and each subunit folds back on itself, translocating a potential membrane-interaction peptide from one end of the spike to the other. This rearrangement resembles the conformational transitions of membrane fusion proteins of enveloped viruses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Capsid Proteins / chemistry*
  • Capsid Proteins / metabolism*
  • Capsid Proteins / ultrastructure
  • Chymotrypsin / metabolism
  • Cryoelectron Microscopy
  • Membrane Fusion*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Rotavirus / chemistry*
  • Trypsin / metabolism
  • Viral Fusion Proteins / chemistry
  • Viral Fusion Proteins / metabolism
  • Viral Fusion Proteins / ultrastructure
  • Viral Proteins / chemistry*
  • Viral Proteins / metabolism*
  • Viral Proteins / ultrastructure


  • Capsid Proteins
  • VP4 protein, Rotavirus
  • Viral Fusion Proteins
  • Viral Proteins
  • Chymotrypsin
  • Trypsin

Associated data

  • PDB/1SLQ