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.
Dormitzer
Philip R
PR
Department of Pediatrics, Harvard Medical School, and the Laboratory of Molecular Medicine, Children's Hospital, Boston, Massachusetts 02115, USA. dormitze@crystal.harvard.edu
Nason
Emma B
EB
Prasad
B V V
BV
Harrison
Stephen C
SC
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