Effect of oculopharyngeal muscular dystrophy‐associated extension of seven alanines on the fibrillation properties of the N‐terminal domain of PABPN1
Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disease that usually manifests itself within the fifth decade. The most prominent symptoms are progressive ptosis, dysphagia, and proximal limb muscle weakness. The disorder is caused by trinucleotide (GCG) expansions in the N‐termin...
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description | Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disease that usually manifests itself within the fifth decade. The most prominent symptoms are progressive ptosis, dysphagia, and proximal limb muscle weakness. The disorder is caused by trinucleotide (GCG) expansions in the N‐terminal part of the poly(A)‐binding protein 1 (PABPN1) that result in the extension of a 10‐alanine segment by up to seven more alanines. In patients, biopsy material displays intranuclear inclusions consisting primarily of PABPN1. Poly l‐alanine‐dependent fibril formation was studied using the recombinant N‐terminal domain of PABPN1. In the case of the protein fragment with the expanded poly l‐alanine sequence [N‐(+7)Ala], fibril formation could be induced by low amounts of fragmented fibrils serving as seeds. Besides homologous seeds, seeds derived from fibrils of the wild‐type fragment (N‐WT) also accelerated fibril formation of N‐(+7)Ala in a concentration‐dependent manner. Seed‐induced fibrillation of N‐WT was considerably slower than that of N‐(+7)Ala. Using atomic force microscopy, differences in fibril morphologies between N‐WT and N‐(+7)Ala were detected. Furthermore, fibrils of N‐WT showed a lower resistance against solubilization with the chaotropic agent guanidinium thiocyanate than those from N‐(+7)Ala. Our data clearly reveal biophysical differences between fibrils of the two variants that are likely caused by divergent fibril structures. |
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The most prominent symptoms are progressive ptosis, dysphagia, and proximal limb muscle weakness. The disorder is caused by trinucleotide (GCG) expansions in the N‐terminal part of the poly(A)‐binding protein 1 (PABPN1) that result in the extension of a 10‐alanine segment by up to seven more alanines. In patients, biopsy material displays intranuclear inclusions consisting primarily of PABPN1. Poly l‐alanine‐dependent fibril formation was studied using the recombinant N‐terminal domain of PABPN1. In the case of the protein fragment with the expanded poly l‐alanine sequence [N‐(+7)Ala], fibril formation could be induced by low amounts of fragmented fibrils serving as seeds. Besides homologous seeds, seeds derived from fibrils of the wild‐type fragment (N‐WT) also accelerated fibril formation of N‐(+7)Ala in a concentration‐dependent manner. Seed‐induced fibrillation of N‐WT was considerably slower than that of N‐(+7)Ala. Using atomic force microscopy, differences in fibril morphologies between N‐WT and N‐(+7)Ala were detected. Furthermore, fibrils of N‐WT showed a lower resistance against solubilization with the chaotropic agent guanidinium thiocyanate than those from N‐(+7)Ala. Our data clearly reveal biophysical differences between fibrils of the two variants that are likely caused by divergent fibril structures.</description><identifier>ISSN: 1742-464X</identifier><identifier>EISSN: 1742-4658</identifier><identifier>DOI: 10.1111/j.1742-4658.2006.05595.x</identifier><identifier>PMID: 17229142</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>AFM ; Alanine - chemistry ; alanine expansions ; amyloid‐like ; Chromatography, High Pressure Liquid ; Genetic disorders ; Humans ; Kinetics ; kinetics of fibril formation ; Microscopy, Atomic Force ; Molecular biology ; Muscular dystrophy ; Muscular Dystrophy, Oculopharyngeal - metabolism ; OPMD ; Peptides - chemistry ; Poly(A)-Binding Protein I - chemistry ; Poly(A)-Binding Protein I - physiology ; Protein Structure, Tertiary ; Proteins ; Recombinant Proteins - chemistry ; Time Factors ; Trinucleotide Repeat Expansion</subject><ispartof>The FEBS journal, 2007-01, Vol.274 (2), p.346-355</ispartof><rights>2007 The Authors Journal compilation 2007 FEBS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4455-788b01edca79816ad9e6a953c0921c9fa56f163652d517da685e84640bfd04983</citedby><cites>FETCH-LOGICAL-c4455-788b01edca79816ad9e6a953c0921c9fa56f163652d517da685e84640bfd04983</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1742-4658.2006.05595.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1742-4658.2006.05595.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17229142$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lodderstedt, Grit</creatorcontrib><creatorcontrib>Hess, Simone</creatorcontrib><creatorcontrib>Hause, Gerd</creatorcontrib><creatorcontrib>Scheuermann, Till</creatorcontrib><creatorcontrib>Scheibel, Thomas</creatorcontrib><creatorcontrib>Schwarz, Elisabeth</creatorcontrib><title>Effect of oculopharyngeal muscular dystrophy‐associated extension of seven alanines on the fibrillation properties of the N‐terminal domain of PABPN1</title><title>The FEBS journal</title><addtitle>FEBS J</addtitle><description>Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disease that usually manifests itself within the fifth decade. The most prominent symptoms are progressive ptosis, dysphagia, and proximal limb muscle weakness. The disorder is caused by trinucleotide (GCG) expansions in the N‐terminal part of the poly(A)‐binding protein 1 (PABPN1) that result in the extension of a 10‐alanine segment by up to seven more alanines. In patients, biopsy material displays intranuclear inclusions consisting primarily of PABPN1. Poly l‐alanine‐dependent fibril formation was studied using the recombinant N‐terminal domain of PABPN1. In the case of the protein fragment with the expanded poly l‐alanine sequence [N‐(+7)Ala], fibril formation could be induced by low amounts of fragmented fibrils serving as seeds. Besides homologous seeds, seeds derived from fibrils of the wild‐type fragment (N‐WT) also accelerated fibril formation of N‐(+7)Ala in a concentration‐dependent manner. Seed‐induced fibrillation of N‐WT was considerably slower than that of N‐(+7)Ala. Using atomic force microscopy, differences in fibril morphologies between N‐WT and N‐(+7)Ala were detected. Furthermore, fibrils of N‐WT showed a lower resistance against solubilization with the chaotropic agent guanidinium thiocyanate than those from N‐(+7)Ala. Our data clearly reveal biophysical differences between fibrils of the two variants that are likely caused by divergent fibril structures.</description><subject>AFM</subject><subject>Alanine - chemistry</subject><subject>alanine expansions</subject><subject>amyloid‐like</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Genetic disorders</subject><subject>Humans</subject><subject>Kinetics</subject><subject>kinetics of fibril formation</subject><subject>Microscopy, Atomic Force</subject><subject>Molecular biology</subject><subject>Muscular dystrophy</subject><subject>Muscular Dystrophy, Oculopharyngeal - metabolism</subject><subject>OPMD</subject><subject>Peptides - chemistry</subject><subject>Poly(A)-Binding Protein I - chemistry</subject><subject>Poly(A)-Binding Protein I - physiology</subject><subject>Protein Structure, Tertiary</subject><subject>Proteins</subject><subject>Recombinant Proteins - chemistry</subject><subject>Time Factors</subject><subject>Trinucleotide Repeat Expansion</subject><issn>1742-464X</issn><issn>1742-4658</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcGOFCEQhjtG466rr2CIB2_TAg00XEx2N7Nqslk3URNvhKELl0l3MwKtMzcfwauv55NIz0zWxJNcIPV_9VOpv6oQwTUp59W6Ji2jCya4rCnGosacK15vH1Sn98LD-zf7fFI9SWmNccOZUo-rE9JSqgijp9WvpXNgMwoOBTv1YXNn4m78AqZHw5RKxUTU7VKORdn9_vHTpBSsNxk6BNsMY_JhnJsTfIMRmd6MfoSESjHfAXJ-FX3fmzxTm-IBMftZdnv5phhmiIMfy3ddGIzfe92eX9zekKfVI2f6BM-O91n16Wr58fLt4vr9m3eX59cLyxjni1bKFSbQWdMqSYTpFAijeGOxosQqZ7hwRDSC046TtjNCcpBlJ3jlOsyUbM6qlwffMt_XCVLWg08WytQjhClpIRWVomkL-OIfcB2mWEZPmmJGmJSUF0geIBtDShGc3kQ_lJ1qgvWcnV7rORY9R6Tn7PQ-O70trc-P_tNqgO5v4zGsArw-AN99D7v_NtZXy4sP87P5A49QrH0</recordid><startdate>200701</startdate><enddate>200701</enddate><creator>Lodderstedt, Grit</creator><creator>Hess, Simone</creator><creator>Hause, Gerd</creator><creator>Scheuermann, Till</creator><creator>Scheibel, Thomas</creator><creator>Schwarz, Elisabeth</creator><general>Blackwell Publishing Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200701</creationdate><title>Effect of oculopharyngeal muscular dystrophy‐associated extension of seven alanines on the fibrillation properties of the N‐terminal domain of PABPN1</title><author>Lodderstedt, Grit ; Hess, Simone ; Hause, Gerd ; Scheuermann, Till ; Scheibel, Thomas ; Schwarz, Elisabeth</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4455-788b01edca79816ad9e6a953c0921c9fa56f163652d517da685e84640bfd04983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>AFM</topic><topic>Alanine - chemistry</topic><topic>alanine expansions</topic><topic>amyloid‐like</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Genetic disorders</topic><topic>Humans</topic><topic>Kinetics</topic><topic>kinetics of fibril formation</topic><topic>Microscopy, Atomic Force</topic><topic>Molecular biology</topic><topic>Muscular dystrophy</topic><topic>Muscular Dystrophy, Oculopharyngeal - metabolism</topic><topic>OPMD</topic><topic>Peptides - chemistry</topic><topic>Poly(A)-Binding Protein I - chemistry</topic><topic>Poly(A)-Binding Protein I - physiology</topic><topic>Protein Structure, Tertiary</topic><topic>Proteins</topic><topic>Recombinant Proteins - chemistry</topic><topic>Time Factors</topic><topic>Trinucleotide Repeat Expansion</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lodderstedt, Grit</creatorcontrib><creatorcontrib>Hess, Simone</creatorcontrib><creatorcontrib>Hause, Gerd</creatorcontrib><creatorcontrib>Scheuermann, Till</creatorcontrib><creatorcontrib>Scheibel, Thomas</creatorcontrib><creatorcontrib>Schwarz, Elisabeth</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The FEBS journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lodderstedt, Grit</au><au>Hess, Simone</au><au>Hause, Gerd</au><au>Scheuermann, Till</au><au>Scheibel, Thomas</au><au>Schwarz, Elisabeth</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of oculopharyngeal muscular dystrophy‐associated extension of seven alanines on the fibrillation properties of the N‐terminal domain of PABPN1</atitle><jtitle>The FEBS journal</jtitle><addtitle>FEBS J</addtitle><date>2007-01</date><risdate>2007</risdate><volume>274</volume><issue>2</issue><spage>346</spage><epage>355</epage><pages>346-355</pages><issn>1742-464X</issn><eissn>1742-4658</eissn><abstract>Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disease that usually manifests itself within the fifth decade. The most prominent symptoms are progressive ptosis, dysphagia, and proximal limb muscle weakness. The disorder is caused by trinucleotide (GCG) expansions in the N‐terminal part of the poly(A)‐binding protein 1 (PABPN1) that result in the extension of a 10‐alanine segment by up to seven more alanines. In patients, biopsy material displays intranuclear inclusions consisting primarily of PABPN1. Poly l‐alanine‐dependent fibril formation was studied using the recombinant N‐terminal domain of PABPN1. In the case of the protein fragment with the expanded poly l‐alanine sequence [N‐(+7)Ala], fibril formation could be induced by low amounts of fragmented fibrils serving as seeds. Besides homologous seeds, seeds derived from fibrils of the wild‐type fragment (N‐WT) also accelerated fibril formation of N‐(+7)Ala in a concentration‐dependent manner. Seed‐induced fibrillation of N‐WT was considerably slower than that of N‐(+7)Ala. Using atomic force microscopy, differences in fibril morphologies between N‐WT and N‐(+7)Ala were detected. Furthermore, fibrils of N‐WT showed a lower resistance against solubilization with the chaotropic agent guanidinium thiocyanate than those from N‐(+7)Ala. Our data clearly reveal biophysical differences between fibrils of the two variants that are likely caused by divergent fibril structures.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>17229142</pmid><doi>10.1111/j.1742-4658.2006.05595.x</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | AFM Alanine - chemistry alanine expansions amyloid‐like Chromatography, High Pressure Liquid Genetic disorders Humans Kinetics kinetics of fibril formation Microscopy, Atomic Force Molecular biology Muscular dystrophy Muscular Dystrophy, Oculopharyngeal - metabolism OPMD Peptides - chemistry Poly(A)-Binding Protein I - chemistry Poly(A)-Binding Protein I - physiology Protein Structure, Tertiary Proteins Recombinant Proteins - chemistry Time Factors Trinucleotide Repeat Expansion |
title | Effect of oculopharyngeal muscular dystrophy‐associated extension of seven alanines on the fibrillation properties of the N‐terminal domain of PABPN1 |
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