A Rotavirus Spike Protein Conformational Intermediate Binds Lipid Bilayers
| Autor: | Stephen C. Harrison, Philip R. Dormitzer, Shane D. Trask, Irene S. Kim |
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| Rok vydání: | 2010 |
| Předmět: |
Models
Molecular Rotavirus Conformational change Protein Conformation viruses Lipid Bilayers Immunology Viral Nonstructural Proteins Models Biological Microbiology Cell Line Virology medicine Animals Chymotrypsin Trypsin Lipid bilayer Host cell membrane Liposome biology Structure and Assembly Virus Internalization Antibodies Neutralizing Macaca mulatta Fusion protein Peptide Fragments Recombinant Proteins Biochemistry Cytoplasm Insect Science Liposomes biology.protein Biophysics Protein Binding medicine.drug |
| Zdroj: | Journal of Virology. 84:1764-1770 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.01682-09 |
| Popis: | During rotavirus entry, a virion penetrates a host cell membrane, sheds its outer capsid proteins, and releases a transcriptionally active subviral particle into the cytoplasm. VP5*, the rotavirus protein believed to interact with the membrane bilayer, is a tryptic cleavage product of the outer capsid spike protein, VP4. When a rotavirus particle uncoats, VP5* folds back, in a rearrangement that resembles the fusogenic conformational changes in enveloped-virus fusion proteins. We present direct experimental evidence that this rearrangement leads to membrane binding. VP5* does not associate with liposomes when mounted as part of the trypsin-primed spikes on intact virions, nor does it do so after it has folded back into a stably trimeric, low-energy state. But it does bind liposomes when they are added to virions before uncoating, and VP5* rearrangement is then triggered by addition of EDTA. The presence of liposomes during the rearrangement enhances the otherwise inefficient VP5* conformational change. A VP5* fragment, VP5CT, produced from monomeric recombinant VP4 by successive treatments with chymotrypsin and trypsin, also binds liposomes only when the proteolysis proceeds in their presence. A monoclonal antibody that neutralizes infectivity by blocking a postattachment entry event also blocks VP5* liposome association. We propose that VP5* binds lipid bilayers in an intermediate conformational state, analogous to the extended intermediate conformation of enveloped-virus fusion proteins. |
| Databáze: | OpenAIRE |
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