Recombinant PrPSc shares structural features with brain-derived PrPSc: Insights from limited proteolysis
Publication Date
January 31, 2018
Authors
Alejandro M. Sevillano, Natalia Fernández Borges, Neelam Younas, Fei Wang, et al
Volume
14
Issue
1
Pages
e1006797
DOI
https://dx.plos.org/10.1371/journal.ppat.1006797
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1006797
Scopus
85041510935
Mendeley
http://www.mendeley.com/research/recombinant-prpscshares-structural-features-brainderived-prpsc-insights-limited-proteolysis
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Mendeley | Further Information

{"title"=>"Recombinant PrPScshares structural features with brain-derived PrPSc: Insights from limited proteolysis", "type"=>"journal", "authors"=>[{"first_name"=>"Alejandro M.", "last_name"=>"Sevillano", "scopus_author_id"=>"57191413491"}, {"first_name"=>"Natalia", "last_name"=>"Fernández-Borges", "scopus_author_id"=>"57191783529"}, {"first_name"=>"Neelam", "last_name"=>"Younas", "scopus_author_id"=>"57200530524"}, {"first_name"=>"Fei", "last_name"=>"Wang", "scopus_author_id"=>"57200536500"}, {"first_name"=>"Saioa", "last_name"=>"R. Elezgarai", "scopus_author_id"=>"57200530313"}, {"first_name"=>"Susana", "last_name"=>"Bravo", "scopus_author_id"=>"7005427162"}, {"first_name"=>"Ester", "last_name"=>"Vázquez-Fernández", "scopus_author_id"=>"54382506800"}, {"first_name"=>"Isaac", "last_name"=>"Rosa", "scopus_author_id"=>"35741727700"}, {"first_name"=>"Hasier", "last_name"=>"Eraña", "scopus_author_id"=>"55497437900"}, {"first_name"=>"David", "last_name"=>"Gil", "scopus_author_id"=>"57195492947"}, {"first_name"=>"Sonia", "last_name"=>"Veiga", "scopus_author_id"=>"57198052233"}, {"first_name"=>"Enric", "last_name"=>"Vidal", "scopus_author_id"=>"8652854100"}, {"first_name"=>"Melissa L.", "last_name"=>"Erickson-Beltran", "scopus_author_id"=>"57194754373"}, {"first_name"=>"Esteban", "last_name"=>"Guitián", "scopus_author_id"=>"54881765300"}, {"first_name"=>"Christopher J.", "last_name"=>"Silva", "scopus_author_id"=>"57200576406"}, {"first_name"=>"Romolo", "last_name"=>"Nonno", "scopus_author_id"=>"6602638620"}, {"first_name"=>"Jiyan", "last_name"=>"Ma", "scopus_author_id"=>"7406201985"}, {"first_name"=>"Joaquín", "last_name"=>"Castilla", "scopus_author_id"=>"8851950500"}, {"first_name"=>"Jesús", "last_name"=>"R. Requena", "scopus_author_id"=>"57200532814"}], "year"=>2018, "source"=>"PLoS Pathogens", "identifiers"=>{"pui"=>"620571530", "pmid"=>"29385212", "doi"=>"10.1371/journal.ppat.1006797", "issn"=>"15537374", "scopus"=>"2-s2.0-85041510935", "sgr"=>"85041510935"}, "id"=>"ffe31ec1-70e8-30c2-92d3-a3b8d0f52e69", "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.", "link"=>"http://www.mendeley.com/research/recombinant-prpscshares-structural-features-brainderived-prpsc-insights-limited-proteolysis", "reader_count"=>3, "reader_count_by_academic_status"=>{"Researcher"=>2, "Student > Ph. D. Student"=>1}, "reader_count_by_user_role"=>{"Researcher"=>2, "Student > Ph. D. Student"=>1}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>2, "Biochemistry, Genetics and Molecular Biology"=>1}, "reader_count_by_subdiscipline"=>{"Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "group_count"=>0}

Scopus | Further Information

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