{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T01:51:24Z","timestamp":1716515484317},"reference-count":37,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2011,10,10]],"date-time":"2011-10-10T00:00:00Z","timestamp":1318204800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:p>The risk of acquiring variant Creutzfeldt\u2013Jakob disease is closely related to polymorphism at codon\u2003129 of the human prion gene, because almost all variant Creutzfeldt\u2013Jakob disease patients are Met\/Met homozygotes. Although animal transmission experiments corroborated this seeding discrimination, the origin of the differential seeding efficiency of the bovine prion seed for human codon\u2003129 polymorphism remained elusive. Here, we used a short prion protein (PrP) peptide as a model system to test whether seeding discrimination can be found in this simple system. We used a previously developed \u2018seed\u2010titration method\u2019 and time\u2010resolved CD spectroscopy to compare sequence\u2010dependent seeding efficiency regarding codon\u2003129 polymorphism. Our results showed that the Met\u2192Val substitution on the human PrP (huPrP) peptide decreased seeding efficiency by 10 times when fibrils formed from bovine PrP (bPrP) peptide were used as the seed. To explore whether the different seeding barrier is due to the chemical and structural properties of Met and Val or whether another residue is involved in this peptide model, we constructed three bPrP mutants, V112M, L138I and N143S, in each of which one residue was replaced by the corresponding human residue. Our data showed that Leu138 in the bPrP seed might be the key residue causing the different seeding efficiencies related to 129M\/V polymorphism and the interference effect of huPrP129V in the huPrP129M\/V mixture. We propose a \u2018surface competition hypothesis\u2019 to explain the big seeding barrier caused by 129V in the PrP peptide seeding experiment.<\/jats:p><jats:p><jats:bold>Structured digital abstract<\/jats:bold><\/jats:p><jats:p><jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>\u2002<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.uniprot.org\/uniprot\/P04156\">huPrP<\/jats:ext-link>\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ebi.ac.uk\/ontology-lookup\/?termId=MI:0191\">aggregates<\/jats:ext-link> with <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.uniprot.org\/uniprot\/P10279\">bPrP<\/jats:ext-link>\u2003by\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ebi.ac.uk\/ontology-lookup\/?termId=MI:0016\">circular dichroism<\/jats:ext-link>\u2003(View Interaction\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/mint.bio.uniroma2.it\/mint\/search\/interaction.do?interactionAc=MINT-8204296\">1<\/jats:ext-link>,\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/mint.bio.uniroma2.it\/mint\/search\/interaction.do?interactionAc=MINT-8204515\">2<\/jats:ext-link>)<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>\u2002<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.uniprot.org\/uniprot\/P10279\">bPrP<\/jats:ext-link>\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ebi.ac.uk\/ontology-lookup\/?termId=MI:0191\">aggregates<\/jats:ext-link> with\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.uniprot.org\/uniprot\/P10279\">bPrP<\/jats:ext-link>\u2003by\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ebi.ac.uk\/ontology-lookup\/?termId=MI:0016\">circular dichroism<\/jats:ext-link>\u2003(<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/mint.bio.uniroma2.it\/mint\/search\/interaction.do?interactionAc=MINT-8204246\">View interaction<\/jats:ext-link>)<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>\u2002<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.uniprot.org\/uniprot\/P10279\">bPrP<\/jats:ext-link>\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ebi.ac.uk\/ontology-lookup\/?termId=MI:0191\">aggregates<\/jats:ext-link> with\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.uniprot.org\/uniprot\/P10279\">bPrP<\/jats:ext-link>\u2003by\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ebi.ac.uk\/ontology-lookup\/?termId=MI:0040\">electron microscopy<\/jats:ext-link>\u2003(<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/mint.bio.uniroma2.it\/mint\/search\/interaction.do?interactionAc=MINT-8204173\">View interaction<\/jats:ext-link>)<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>\u2002<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.uniprot.org\/uniprot\/P10279\">bPrP<\/jats:ext-link>\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ebi.ac.uk\/ontology-lookup\/?termId=MI:0191\">aggregates<\/jats:ext-link>\u2003with\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.uniprot.org\/uniprot\/P10279\">bPrP<\/jats:ext-link>\u2003by\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ebi.ac.uk\/ontology-lookup\/?termId=MI:0051\">fluorescence technology<\/jats:ext-link>\u2003(<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/mint.bio.uniroma2.it\/mint\/search\/interaction.do?interactionAc=MINT-8204199\">View interaction<\/jats:ext-link>)<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>\u2002<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.uniprot.org\/uniprot\/P04156\">huPrP<\/jats:ext-link>\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ebi.ac.uk\/ontology-lookup\/?termId=MI:0191\">aggregates<\/jats:ext-link>\u2003with\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.uniprot.org\/uniprot\/P04156\">huPrP<\/jats:ext-link>\u2003by\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ebi.ac.uk\/ontology-lookup\/?termId=MI:0040\">electron microscopy<\/jats:ext-link>\u2003(<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/mint.bio.uniroma2.it\/mint\/search\/interaction.do?interactionAc=MINT-8204160\">View interaction<\/jats:ext-link>)<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>\u2002<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.uniprot.org\/uniprot\/P04156\">huPrP<\/jats:ext-link>\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ebi.ac.uk\/ontology-lookup\/?termId=MI:0191\">aggregates<\/jats:ext-link>\u2003with\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.uniprot.org\/uniprot\/P04156\">huPrP<\/jats:ext-link>\u2003by\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ebi.ac.uk\/ontology-lookup\/?termId=MI:0051\">fluorescence technology<\/jats:ext-link>\u2003(<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/mint.bio.uniroma2.it\/mint\/search\/interaction.do?interactionAc=MINT-8204188\">View interaction<\/jats:ext-link>)<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>\u2002<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.uniprot.org\/uniprot\/P04156\">huPrP<\/jats:ext-link>\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ebi.ac.uk\/ontology-lookup\/?termId=MI:0191\">aggregates<\/jats:ext-link>\u2003with\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.uniprot.org\/uniprot\/P04156\">huPrP<\/jats:ext-link>\u2003by\u2003<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ebi.ac.uk\/ontology-lookup\/?termId=MI:0016\">circular dichroism<\/jats:ext-link>\u2003(<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/mint.bio.uniroma2.it\/mint\/search\/interaction.do?interactionAc=MINT-8204222\">View interaction<\/jats:ext-link>)<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p>","DOI":"10.1111\/j.1742-4658.2011.08353.x","type":"journal-article","created":{"date-parts":[[2011,9,16]],"date-time":"2011-09-16T00:41:38Z","timestamp":1316133698000},"page":"4351-4361","source":"Crossref","is-referenced-by-count":7,"title":["Leu138 in bovine prion peptide fibrils is involved in seeding discrimination related to codon\u2003129\u2003M\/V polymorphism in the prion peptide seeding experiment"],"prefix":"10.1111","volume":"278","author":[{"given":"Tai\u2010Yan","family":"Liao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lily Y.\u2010L.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita P.\u2010Y.","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,10,10]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20025"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6801762"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80596-6"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.24.11160"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.7.2608-2616.2001"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi9923353"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-440X(97)80007-3"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-0278(96)00007-7"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(04)00155-8"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.01.034"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.9.3923"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0667413"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/40876"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(06)70413-6"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1103932"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.01.149"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)63366-1"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tmrv.2007.09.003"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61568-3"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.64.12.1780"},{"key":"e_1_2_6_22_2","volume-title":"Proteins: Structures and Molecular Properties","author":"Creighton 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