dc.contributor.author |
Ciric, Danica
|
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dc.contributor.author |
Richard, Charles-Adrien
|
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dc.contributor.author |
Moudjou, Mohammed
|
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dc.contributor.author |
Chapuis, Jérome
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dc.contributor.author |
Sibille, Pierre
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dc.contributor.author |
Daude, Nathalie
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dc.contributor.author |
Westaway, David
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dc.contributor.author |
Adrover, Miquel
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dc.contributor.author |
Béringue, Vient
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dc.contributor.author |
Martin, Davy
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dc.contributor.author |
Rezaei, Human
|
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dc.date.accessioned |
2020-04-28T06:45:55Z |
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dc.identifier.uri |
http://hdl.handle.net/11201/152159 |
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dc.description.abstract |
[eng Prion diseases are characterised by conformational changes of a cellular prion protein (PrPC) into a β-sheet-enriched and aggregated conformer (PrPSc). Shadoo (Sho), a member of the prion protein family, is expressed in the central nervous system (CNS) and is highly conserved among vertebrates. Based on histo-anatomical co-localisation and sequence similarities, it is suspected that Sho and PrP may be functionally related. The down-regulation of Sho expression during prion pathology and the direct interaction between Sho and PrP, as revealed by the two-hybrid analysis, suggest a relationship between Sho and prion replication. Using biochemical and biophysical approaches, we demonstrate that Sho forms a 1:1 complex with full-length PrP, with a Kd in the micromolar range, and this interaction consequently modifies the PrP folding pathway. Using a truncated PrP that mimics the C1 fragment, an allosteric binding behaviour with a Hill number of 4 was observed, suggesting that at least a tetramerisation state occurs. Cell-based prion titration assay performed with different concentrations of Sho revealed an increase in the PrPSc conversion rate in the presence of Sho. Collectively, our observations suggest that Sho can affect the prion replication process by 1) acting as a holdase and 2) interfering with the dominant-negative inhibitor effect of the C1 fragment. |
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dc.format |
application/pdf |
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dc.relation.isformatof |
Versió postprint del document publicat a: https://doi.org/10.1128/JVI.03429-14 |
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dc.relation.ispartof |
Journal of Virology, 2015, vol. 89, num. 12, p. 6287-6293 |
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dc.rights |
(c) American Society for Microbiology, 2015 |
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dc.subject.classification |
54 - Química |
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dc.subject.other |
54 - Chemistry. Crystallography. Mineralogy |
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dc.title |
Interaction between Shadoo and PrP affects the PrP-folding pathway |
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dc.type |
info:eu-repo/semantics/article |
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dc.type |
info:eu-repo/semantics/acceptedVersion |
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dc.date.updated |
2020-04-28T06:45:55Z |
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dc.date.embargoEndDate |
info:eu-repo/date/embargoEnd/2026-12-31 |
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dc.embargo |
2026-12-31 |
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dc.subject.keywords |
Prion protein |
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dc.subject.keywords |
biological-physical interactions |
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dc.subject.keywords |
cell toxicity |
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dc.rights.accessRights |
info:eu-repo/semantics/embargoedAccess |
|
dc.identifier.doi |
https://doi.org/10.1128/JVI.03429-14 |
|