Structural rearrangements in the membrane penetration protein of a non-enveloped virus.
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.
Department of Pediatrics, Harvard Medical School, and the Laboratory of Molecular Medicine, Children's Hospital, Boston, Massachusetts 02115, USA. dormitze@crystal.harvard.edu
Philip R
PR
Dormitzer
Emma B
EB
Nason
B V V
BV
Prasad
Stephen C
SC
Harrison
D000595:Amino Acid Sequence; D036022:Capsid Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D002918:Chymotrypsin / Q000378:metabolism; D020285:Cryoelectron Microscopy; D008561:Membrane Fusion; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012401:Rotavirus / Q000737:chemistry*; D014357:Trypsin / Q000378:metabolism; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure
D036022:Capsid Proteins; C060339:VP4 protein, Rotavirus; D014760:Viral Fusion Proteins; D014764:Viral Proteins; D002918:Chymotrypsin; D014357:Trypsin