The N-terminal sequence of prion protein consists an epitope specific to the abnormal isoform of prion protein (PrP(Sc))
The conformation of abnormal prion protein (PrP(Sc)) differs from that of cellular prion protein (PrP(C)), but the precise characteristics of PrP(Sc) remain to be elucidated. To clarify the properties of native PrP(Sc), we attempted to generate novel PrP(Sc)-specific monoclonal antibodies (mAbs) by...
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| creator | Masujin, Kentaro Kaku-Ushiki, Yuko Miwa, Ritsuko Okada, Hiroyuki Shimizu, Yoshihisa Kasai, Kazuo Matsuura, Yuichi Yokoyama, Takashi |
| description | The conformation of abnormal prion protein (PrP(Sc)) differs from that of cellular prion protein (PrP(C)), but the precise characteristics of PrP(Sc) remain to be elucidated. To clarify the properties of native PrP(Sc), we attempted to generate novel PrP(Sc)-specific monoclonal antibodies (mAbs) by immunizing PrP-deficient mice with intact PrP(Sc) purified from bovine spongiform encephalopathy (BSE)-affected mice. The generated mAbs 6A12 and 8D5 selectivity precipitated PrP(Sc) from the brains of prion-affected mice, sheep, and cattle, but did not precipitate PrP(C) from the brains of healthy animals. In histopathological analysis, mAbs 6A12 and 8D5 strongly reacted with prion-affected mouse brains but not with unaffected mouse brains without antigen retrieval. Epitope analysis revealed that mAbs 8D5 and 6A12 recognized the PrP subregions between amino acids 31-39 and 41-47, respectively. This indicates that a PrP(Sc)-specific epitope exists in the N-terminal region of PrP(Sc), and mAbs 6A12 and 8D5 are powerful tools with which to detect native and intact PrP(Sc). We found that the ratio of proteinase K (PK)-sensitive PrP(Sc) to PK-resistant PrP(Sc) was constant throughout the disease time course. |
| doi_str_mv | 10.1371/journal.pone.0058013 |
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To clarify the properties of native PrP(Sc), we attempted to generate novel PrP(Sc)-specific monoclonal antibodies (mAbs) by immunizing PrP-deficient mice with intact PrP(Sc) purified from bovine spongiform encephalopathy (BSE)-affected mice. The generated mAbs 6A12 and 8D5 selectivity precipitated PrP(Sc) from the brains of prion-affected mice, sheep, and cattle, but did not precipitate PrP(C) from the brains of healthy animals. In histopathological analysis, mAbs 6A12 and 8D5 strongly reacted with prion-affected mouse brains but not with unaffected mouse brains without antigen retrieval. Epitope analysis revealed that mAbs 8D5 and 6A12 recognized the PrP subregions between amino acids 31-39 and 41-47, respectively. This indicates that a PrP(Sc)-specific epitope exists in the N-terminal region of PrP(Sc), and mAbs 6A12 and 8D5 are powerful tools with which to detect native and intact PrP(Sc). We found that the ratio of proteinase K (PK)-sensitive PrP(Sc) to PK-resistant PrP(Sc) was constant throughout the disease time course.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0058013</identifier><identifier>PMID: 23469131</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Amino Acid Sequence ; Amino acids ; Animals ; Antibodies, Monoclonal - immunology ; Antibody Specificity ; Biology ; Bovine spongiform encephalopathy ; Brain research ; BSE ; Cattle ; Creutzfeldt-Jakob disease ; Encephalopathy ; Endopeptidase K ; Epitope Mapping ; Epitopes ; Female ; Immunization ; Immunoglobulins ; Medicine ; Mice ; Molecular Sequence Data ; Monoclonal antibodies ; Mutation ; Ovis aries ; Pathogenesis ; Prion Diseases - metabolism ; Prion protein ; Protein structure ; Proteinase ; Proteins ; PrPSc Proteins - chemistry ; PrPSc Proteins - immunology ; PrPSc Proteins - metabolism ; Selectivity ; Sheep ; Veterinary Science</subject><ispartof>PloS one, 2013-02, Vol.8 (2), p.e58013-e58013</ispartof><rights>2013 Masujin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Masujin et al 2013 Masujin et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c592t-dd34262078fa645b26aa0eefccc8a5ce8e63e099e5d57bc69aff1498cb2786ea3</citedby><cites>FETCH-LOGICAL-c592t-dd34262078fa645b26aa0eefccc8a5ce8e63e099e5d57bc69aff1498cb2786ea3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585212/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585212/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23469131$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ma, Jiyan</contributor><creatorcontrib>Masujin, Kentaro</creatorcontrib><creatorcontrib>Kaku-Ushiki, Yuko</creatorcontrib><creatorcontrib>Miwa, Ritsuko</creatorcontrib><creatorcontrib>Okada, Hiroyuki</creatorcontrib><creatorcontrib>Shimizu, Yoshihisa</creatorcontrib><creatorcontrib>Kasai, Kazuo</creatorcontrib><creatorcontrib>Matsuura, Yuichi</creatorcontrib><creatorcontrib>Yokoyama, Takashi</creatorcontrib><title>The N-terminal sequence of prion protein consists an epitope specific to the abnormal isoform of prion protein (PrP(Sc))</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The conformation of abnormal prion protein (PrP(Sc)) differs from that of cellular prion protein (PrP(C)), but the precise characteristics of PrP(Sc) remain to be elucidated. To clarify the properties of native PrP(Sc), we attempted to generate novel PrP(Sc)-specific monoclonal antibodies (mAbs) by immunizing PrP-deficient mice with intact PrP(Sc) purified from bovine spongiform encephalopathy (BSE)-affected mice. The generated mAbs 6A12 and 8D5 selectivity precipitated PrP(Sc) from the brains of prion-affected mice, sheep, and cattle, but did not precipitate PrP(C) from the brains of healthy animals. In histopathological analysis, mAbs 6A12 and 8D5 strongly reacted with prion-affected mouse brains but not with unaffected mouse brains without antigen retrieval. Epitope analysis revealed that mAbs 8D5 and 6A12 recognized the PrP subregions between amino acids 31-39 and 41-47, respectively. This indicates that a PrP(Sc)-specific epitope exists in the N-terminal region of PrP(Sc), and mAbs 6A12 and 8D5 are powerful tools with which to detect native and intact PrP(Sc). We found that the ratio of proteinase K (PK)-sensitive PrP(Sc) to PK-resistant PrP(Sc) was constant throughout the disease time course.</description><subject>Amino Acid Sequence</subject><subject>Amino acids</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibody Specificity</subject><subject>Biology</subject><subject>Bovine spongiform encephalopathy</subject><subject>Brain research</subject><subject>BSE</subject><subject>Cattle</subject><subject>Creutzfeldt-Jakob disease</subject><subject>Encephalopathy</subject><subject>Endopeptidase K</subject><subject>Epitope Mapping</subject><subject>Epitopes</subject><subject>Female</subject><subject>Immunization</subject><subject>Immunoglobulins</subject><subject>Medicine</subject><subject>Mice</subject><subject>Molecular Sequence Data</subject><subject>Monoclonal antibodies</subject><subject>Mutation</subject><subject>Ovis aries</subject><subject>Pathogenesis</subject><subject>Prion Diseases - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Masujin, Kentaro</au><au>Kaku-Ushiki, Yuko</au><au>Miwa, Ritsuko</au><au>Okada, Hiroyuki</au><au>Shimizu, Yoshihisa</au><au>Kasai, Kazuo</au><au>Matsuura, Yuichi</au><au>Yokoyama, Takashi</au><au>Ma, Jiyan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The N-terminal sequence of prion protein consists an epitope specific to the abnormal isoform of prion protein (PrP(Sc))</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-02-28</date><risdate>2013</risdate><volume>8</volume><issue>2</issue><spage>e58013</spage><epage>e58013</epage><pages>e58013-e58013</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The conformation of abnormal prion protein (PrP(Sc)) differs from that of cellular prion protein (PrP(C)), but the precise characteristics of PrP(Sc) remain to be elucidated. To clarify the properties of native PrP(Sc), we attempted to generate novel PrP(Sc)-specific monoclonal antibodies (mAbs) by immunizing PrP-deficient mice with intact PrP(Sc) purified from bovine spongiform encephalopathy (BSE)-affected mice. The generated mAbs 6A12 and 8D5 selectivity precipitated PrP(Sc) from the brains of prion-affected mice, sheep, and cattle, but did not precipitate PrP(C) from the brains of healthy animals. In histopathological analysis, mAbs 6A12 and 8D5 strongly reacted with prion-affected mouse brains but not with unaffected mouse brains without antigen retrieval. Epitope analysis revealed that mAbs 8D5 and 6A12 recognized the PrP subregions between amino acids 31-39 and 41-47, respectively. This indicates that a PrP(Sc)-specific epitope exists in the N-terminal region of PrP(Sc), and mAbs 6A12 and 8D5 are powerful tools with which to detect native and intact PrP(Sc). We found that the ratio of proteinase K (PK)-sensitive PrP(Sc) to PK-resistant PrP(Sc) was constant throughout the disease time course.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23469131</pmid><doi>10.1371/journal.pone.0058013</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Amino Acid Sequence Amino acids Animals Antibodies, Monoclonal - immunology Antibody Specificity Biology Bovine spongiform encephalopathy Brain research BSE Cattle Creutzfeldt-Jakob disease Encephalopathy Endopeptidase K Epitope Mapping Epitopes Female Immunization Immunoglobulins Medicine Mice Molecular Sequence Data Monoclonal antibodies Mutation Ovis aries Pathogenesis Prion Diseases - metabolism Prion protein Protein structure Proteinase Proteins PrPSc Proteins - chemistry PrPSc Proteins - immunology PrPSc Proteins - metabolism Selectivity Sheep Veterinary Science |
| title | The N-terminal sequence of prion protein consists an epitope specific to the abnormal isoform of prion protein (PrP(Sc)) |
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