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http://hdl.handle.net/2445/176729
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DC Field | Value | Language |
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dc.contributor.author | Solsona Sancho, Carles | - |
dc.contributor.author | Kahn, Thomas B. | - |
dc.contributor.author | Badilla, Carmen L. | - |
dc.contributor.author | Álvarez Zaldiernas, Cristina | - |
dc.contributor.author | Blasi Cabús, Joan | - |
dc.contributor.author | Fernández, Julio M. | - |
dc.contributor.author | Alegre-Cebollada, Jorge | - |
dc.date.accessioned | 2021-04-27T13:26:05Z | - |
dc.date.available | 2021-04-27T13:26:05Z | - |
dc.date.issued | 2014-09-26 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | http://hdl.handle.net/2445/176729 | - |
dc.description.abstract | Neurodegenerative diseases share a common characteristic, the presence of intracellular or extracellular deposits of protein aggregates in nervous tissues. Amyotrophic Lateral Sclerosis (ALS) is a severe and fatal neurodegenerative disorder, which affects preferentially motoneurons. Changes in the redox state of superoxide dismutase 1 (SOD1) are associated with the onset and development of familial forms of ALS. In human SOD1 (hSOD1), a conserved disulfide bond and two free cysteine residues can engage in anomalous thiol/disulfide exchange resulting in non-native disulfides, a hallmark of ALS that is related to protein misfolding and aggregation. Because of the many competing reaction pathways, traditional bulk techniques fall short at quantifying individual thiol/disulfide exchange reactions. Here, we adapt recently developed single-bond chemistry techniques to study individual disulfide isomerization reactions in hSOD1. Mechanical unfolding of hSOD1 leads to the formation of a polypeptide loop held by the disulfide. This loop behaves as a molecular jump rope that brings reactive Cys-111 close to the disulfide. Using force-clamp spectroscopy, we monitor nucleophilic attack of Cys-111 at either sulfur of the disulfide and determine the selectivity of the reaction. Disease-causing mutations G93A and A4V show greatly altered reactivity patterns, which may contribute to the progression of familial ALS. | - |
dc.format.extent | 11 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | American Society for Biochemistry and Molecular Biology | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1074/jbc.M114.565333 | - |
dc.relation.ispartof | Journal of Biological Chemistry, 2014, vol. 289, num. 39, p. 26722-26732 | - |
dc.relation.uri | https://doi.org/10.1074/jbc.M114.565333 | - |
dc.rights | (c) American Society for Biochemistry and Molecular Biology, 2014 | - |
dc.source | Articles publicats en revistes (Patologia i Terapèutica Experimental) | - |
dc.subject.classification | Esclerosi lateral amiotròfica | - |
dc.subject.classification | Enzimologia | - |
dc.subject.classification | Cisteïna | - |
dc.subject.classification | Química | - |
dc.subject.other | Amyotrophic lateral sclerosis | - |
dc.subject.other | Enzymology | - |
dc.subject.other | Cysteine | - |
dc.subject.other | Chemistry | - |
dc.title | Altered thiol chemistry in human amyotrophic lateral sclerosis-linked mutants of superoxide dismutase 1 | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 672852 | - |
dc.date.updated | 2021-04-27T13:26:05Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 25096579 | - |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
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672852.pdf | 1.48 MB | Adobe PDF | View/Open |
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