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Lagovirus Non-structural Protein p23: A Putative Viroporin That Interacts With Heat Shock Proteins and Uses a Disulfide Bond for Dimerization.
Smertina, Elena; Carroll, Adam J; Boileau, Joseph; Emmott, Edward; Jenckel, Maria; Vohra, Harpreet; Rolland, Vivien; Hands, Philip; Hayashi, Junna; Neave, Matthew J; Liu, Jian-Wei; Hall, Robyn N; Strive, Tanja; Frese, Michael.
Afiliação
  • Smertina E; Health and Biosecurity, Commonwealth Scientific and Industrial Research Organisation, Canberra, ACT, Australia.
  • Carroll AJ; Faculty of Science and Technology, University of Canberra, Canberra, ACT, Australia.
  • Boileau J; Centre for Invasive Species Solutions, Canberra, ACT, Australia.
  • Emmott E; RSB/RSC Joint Mass Spectrometry Facility, Research School of Chemistry, Australian National University, Acton, ACT, Australia.
  • Jenckel M; RSB/RSC Joint Mass Spectrometry Facility, Research School of Chemistry, Australian National University, Acton, ACT, Australia.
  • Vohra H; Centre for Proteome Research, Department of Biochemistry & Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
  • Rolland V; Health and Biosecurity, Commonwealth Scientific and Industrial Research Organisation, Canberra, ACT, Australia.
  • Hands P; Imaging and Cytometry Facility, John Curtin School of Medical Research, Acton, ACT, Australia.
  • Hayashi J; Agriculture and Food, Commonwealth Scientific and Industrial Research Organisation, Canberra, ACT, Australia.
  • Neave MJ; Agriculture and Food, Commonwealth Scientific and Industrial Research Organisation, Canberra, ACT, Australia.
  • Liu JW; Research School of Chemistry, Australian National University, Acton, ACT, Australia.
  • Hall RN; Australian Centre for Disease Preparedness, Commonwealth Scientific and Industrial Research Organisation, Geelong, VIC, Australia.
  • Strive T; Land and Water, Commonwealth Scientific and Industrial Research Organisation, Canberra, ACT, Australia.
  • Frese M; Health and Biosecurity, Commonwealth Scientific and Industrial Research Organisation, Canberra, ACT, Australia.
Front Microbiol ; 13: 923256, 2022.
Article em En | MEDLINE | ID: mdl-35923397
ABSTRACT
The exact function(s) of the lagovirus non-structural protein p23 is unknown as robust cell culture systems for the Rabbit haemorrhagic disease virus (RHDV) and other lagoviruses have not been established. Instead, a range of in vitro and in silico models have been used to study p23, revealing that p23 oligomerizes, accumulates in the cytoplasm, and possesses a conserved C-terminal region with two amphipathic helices. Furthermore, the positional homologs of p23 in other caliciviruses have been shown to possess viroporin activity. Here, we report on the mechanistic details of p23 oligomerization. Site-directed mutagenesis revealed the importance of an N-terminal cysteine for dimerization. Furthermore, we identified cellular interactors of p23 using stable isotope labeling with amino acids in cell culture (SILAC)-based proteomics; heat shock proteins Hsp70 and 110 interact with p23 in transfected cells, suggesting that they 'chaperone' p23 proteins before their integration into cellular membranes. We investigated changes to the global transcriptome and proteome that occurred in infected rabbit liver tissue and observed changes to the misfolded protein response, calcium signaling, and the regulation of the endoplasmic reticulum (ER) network. Finally, flow cytometry studies indicate slightly elevated calcium concentrations in the cytoplasm of p23-transfected cells. Taken together, accumulating evidence suggests that p23 is a viroporin that might form calcium-conducting channels in the ER membranes.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2022 Tipo de documento: Article