Selenomethionine incorporation into amyloid sequences regulates fibrillogenesis and toxicity

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author Martinez, Javier P.ca
• dc.contributor.author Lisa, Silviaca
• dc.contributor.author Sánchez, Rosaca
• dc.contributor.author Kowalczyk, Wioletaca
• dc.contributor.author Zurita, Estherca
• dc.contributor.author Teixidó, Meritxellca
• dc.contributor.author Giralt, Ernestca
• dc.contributor.author Andreu Martínez, Davidca
• dc.contributor.author Avila, Jesúsca
• dc.contributor.author Gasset, Maríaca
• dc.date.accessioned 2015-05-04T09:34:15Z
• dc.date.available 2015-05-04T09:34:15Z
• dc.date.issued 2011ca
• dc.description.abstract Background: The capacity of a polypeptide chain to engage in an amyloid formation process and cause a conformational disease is contained in its sequence. Some of the sequences undergoing fibrillation contain critical methionine (Met) residues which in vivo can be synthetically substituted by selenomethionine (SeM) and alter their properties. Methodology/Principal Findings: Using peptide synthesis, biophysical techniques and cell viability determinations we have studied the effect of the substitution of methionine (Met) by selenomethionine (SeM) on the fibrillogenesis and toxic properties of Aβ40 and HuPrP(106–140). We have found that the effects display site-specificity and vary from inhibition of fibrillation and decreased toxicity ([SeM35]Aβ40, [SeM129]HuPrP(106–140) and [SeM134]HuPrP(106–140)), retarded assembly, modulation of polymer shape and retention of toxicity ([SeM112]HuPrP(106–140) to absence of effects ([SeM109]HuPrP(106–140)). Conclusions/Significance: This work provides direct evidence that the substitution of Met by SeM in proamyloid sequences has a major impact on their self-assembly and toxic properties, suggesting that the SeM pool can play a major role in dictating the allowance and efficiency of a polypeptide chain to undergo toxic polymerization.en
• dc.description.sponsorship This work was supported in part by gra’ts BFU2009-07975 (MG), BIO2008-04487-CO3-02 (DA) and BIO2008-00799 (EG) from the Spanish Ministry of Science and Innovation, from the Fundación Cien-Fundación Reina Sofia, and from Generalitat de Catalunya (XRB and Grups Consolidats). Wioleta Kowalczyk is supported by a Juan de la Cierva fellowship from the Spanish Ministry of Science and Innovation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscripen
• dc.format.mimetype application/pdfca
• dc.identifier.citation Martínez J, Lisa S, Sánchez R, Kowalczyk W, Zurita E, Teixidó M et al. Selenomethionine incorporation into amyloid sequences regulates fibrillogenesis and toxicity. PLoS ONE. 2011;6(11):e27999. DOI: 10.1371/journal.pone.0027999ca
• dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0027999
• dc.identifier.issn 1932-6203ca
• dc.identifier.uri http://hdl.handle.net/10230/23513
• dc.language.iso engca
• dc.publisher Public Library of Science (PLoS)ca
• dc.relation.ispartof PLoS ONE. 2011;6(11):e27999
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2009-07975
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BIO2008-04487
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BIO2008-00799
• dc.rights © 2011 Martínez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits/nunrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.subject.other Aminoàcidsca
• dc.subject.other Prions -- Aspectes genèticsca
• dc.title Selenomethionine incorporation into amyloid sequences regulates fibrillogenesis and toxicityen
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca