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Recombinant PrPSc shares structural features with brain-derived PrPSc: Insights from limited proteolysis
dc.contributor.author | Sevillano, Alejandro M. | |
dc.contributor.author | Fernández-Borges, Natalia | |
dc.contributor.author | Younas, Neelam | |
dc.contributor.author | Wang, Fei | |
dc.contributor.author | Elezgarai, Saioa R. | |
dc.contributor.author | Bravo, Susana | |
dc.contributor.author | Vázquez-Fernández, Ester | |
dc.contributor.author | Rosa, Isaac | |
dc.contributor.author | Eraña, Hasier | |
dc.contributor.author | Gil, David | |
dc.contributor.author | Veiga, Sonia | |
dc.contributor.author | Vidal, Enric | |
dc.contributor.author | Erickson-Beltran, Melissa L. | |
dc.contributor.author | Requena, Jesús R. | |
dc.contributor.other | Producció Animal | ca |
dc.date.accessioned | 2018-12-03T15:44:34Z | |
dc.date.available | 2018-12-03T15:44:34Z | |
dc.date.issued | 2018-01-31 | |
dc.identifier.citation | Sevillano, Alejandro M., Natalia Fernández-Borges, Neelam Younas, Fei Wang, Saioa R. Elezgarai, Susana Bravo, and Ester Vázquez-Fernández et al. 2018. "Recombinant Prpsc Shares Structural Features With Brain-Derived Prpsc: Insights From Limited Proteolysis". PLOS Pathogens 14 (1): e1006797. Public Library of Science (PLoS). doi:10.1371/journal.ppat.1006797. | ca |
dc.identifier.issn | 1553-7366 | ca |
dc.identifier.uri | http://hdl.handle.net/20.500.12327/100 | |
dc.description.abstract | Very solid evidence suggests that the core of full length PrPSc is a 4-rung β-solenoid, and that individual PrPSc subunits stack to form amyloid fibers. We recently used limited proteolysis to map the β-strands and connecting loops that make up the PrPSc solenoid. Using high resolution SDS-PAGE followed by epitope analysis, and mass spectrometry, we identified positions ~116/118, 133–134, 141, 152–153, 162, 169 and 179 (murine numbering) as Proteinase K (PK) cleavage sites in PrPSc. Such sites likely define loops and/or borders of β-strands, helping us to predict the threading of the β-solenoid. We have now extended this approach to recombinant PrPSc (recPrPSc). The term recPrPSc refers to bona fide recombinant prions prepared by PMCA, exhibiting infectivity with attack rates of ~100%. Limited proteolysis of mouse and bank vole recPrPSc species yielded N-terminally truncated PK-resistant fragments similar to those seen in brain-derived PrPSc, albeit with varying relative yields. Along with these fragments, doubly N- and C-terminally truncated fragments, in particular ~89/97-152, were detected in some recPrPSc preparations; similar fragments are characteristic of atypical strains of brain-derived PrPSc. Our results suggest a shared architecture of recPrPSc and brain PrPSc prions. The observed differences, in particular the distinct yields of specific PK-resistant fragments, are likely due to differences in threading which result in the specific biochemical characteristics of recPrPSc. Furthermore, recombinant PrPSc offers exciting opportunities for structural studies unachievable with brain-derived PrPSc. | ca |
dc.format.extent | 21 | ca |
dc.language.iso | eng | ca |
dc.publisher | Public Library of Science | ca |
dc.relation.ispartof | Plos Pathogens | ca |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.title | Recombinant PrPSc shares structural features with brain-derived PrPSc: Insights from limited proteolysis | ca |
dc.type | info:eu-repo/semantics/article | ca |
dc.description.version | info:eu-repo/semantics/publishedVersion | ca |
dc.rights.accessLevel | info:eu-repo/semantics/openAccess | |
dc.embargo.terms | cap | ca |
dc.relation.projectID | MINECO/Programa Estatal de fomento de la investigación científica y técnica de excelencia/BFU2013-48436-C2-1-P/ES/Decodificando los priones: elucidación de la base estructural de la infectividad de proteinas/ | ca |
dc.relation.projectID | MINECO/Programa Estatal de I+D+I orientada a los retos de la sociedad/AGL2015-65046-C2-1-R/ES/Estudio de los mecanismos moleculares implicados en la diversidad y estabilidad de las cepas priónicas/ | ca |
dc.subject.udc | 619 | ca |
dc.identifier.doi | https://doi.org/10.1371/journal.ppat.1006797 | ca |
dc.contributor.group | Sanitat Animal | ca |
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