AAA ATPase p97/VCP is essential for TRIM21-mediated virus neutralization
| Autor: | Susanna R. Bidgood, Leo C. James, Felix Hauler, Donna L. Mallery, William A. McEwan |
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| Rok vydání: | 2012 |
| Předmět: |
0303 health sciences
Multidisciplinary biology viruses ATPase Valosin-containing protein Molecular biology AAA proteins Virus 03 medical and health sciences 0302 clinical medicine Capsid Proteasome 030220 oncology & carcinogenesis Antibody receptor biology.protein Intracellular 030304 developmental biology |
| Zdroj: | Proceedings of the National Academy of Sciences |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1210659109 |
| Popis: | Tripartite motif-containing 21 (TRIM21) is a cytosolic IgG receptor that mediates intracellular virus neutralization by antibody. TRIM21 targets virions for destruction in the proteasome, but it is unclear how a substrate as large as a viral capsid is degraded. Here, we identify the ATPase p97/valosin-containing protein (VCP), an enzyme with segregase and unfoldase activity, as a key player in this process. Depletion or catalytic inhibition of VCP prevents capsid degradation and reduces neutralization. VCP is required concurrently with the proteasome, as addition of inhibitor after proteasomal degradation has no effect. Moreover, our results suggest that it is the challenging nature of virus as a substrate that necessitates involvement of VCP, since intracellularly expressed IgG Fc is degraded in a VCP-independent manner. These results implicate VCP as an important host factor in antiviral immunity. |
| Databáze: | OpenAIRE |
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