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dc.contributor.author
Sánchez López, Carolina
dc.contributor.author
Fernandez, Claudio Oscar
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dc.contributor.author
Quintanar, Liliana
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dc.date.available
2019-12-05T18:45:24Z
dc.date.issued
2018-01
dc.identifier.citation
Sánchez López, Carolina; Fernandez, Claudio Oscar; Quintanar, Liliana; Neuroprotective alpha-cleavage of the human prion protein significantly impacts Cu(II) coordination at its His111 site; Royal Society of Chemistry; Dalton Transactions; 47; 28; 1-2018; 9274-9282
dc.identifier.issn
1477-9226
dc.identifier.uri
http://hdl.handle.net/11336/91516
dc.description.abstract
The cellular prion protein (PrPC) is a copper binding protein that undergoes post-translational modifications, such as endoproteolytic alpha cleavage, which occurs in the vicinity of the His111 Cu binding site. Alpha cleavage processing of PrPC is considered to be neuroprotective since the cleavage site is located in a region that is key to the conversion of PrPC into the infectious scrapie isoform (PrPSc), yielding a membrane bound C1 fragment of PrPC that still contains His111. In this work, we use hPrP(111-115) fragment as a model peptide to evaluate the impact of alpha cleavage processing of PrPC in its ability to coordinate Cu(ii) ions at His111. By using different spectroscopic techniques such as electronic absorption, circular dichroism, nuclear magnetic resonance, and electron paramagnetic resonance, this study demonstrates that Cu(ii) binding to the cleaved His111 site is highly dependent on Cu and proton concentrations. The imidazole group of His111 and its free NH2 terminus emerge as the main anchoring sites for Cu(ii) coordination, yielding very different complexes from those characterized for the intact His111 site in the full protein. Different Cu(ii) coordination modes that could form with the alpha cleaved PrPC under physiological conditions are identified and characterized. Overall, this study contributes to understand how alpha cleavage processing of PrPC impacts its Cu(ii) binding properties at His111. While the functional implications of Cu binding to the cleaved PrPC remain to be discovered, proteolytic processing of PrPC and its Cu binding features appear to be molecular events that might be strongly linked to its cellular function.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Royal Society of Chemistry
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
PRION
dc.subject
COPPER
dc.subject
AMYLOID
dc.subject.classification
Química Inorgánica y Nuclear
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dc.subject.classification
Ciencias Químicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Neuroprotective alpha-cleavage of the human prion protein significantly impacts Cu(II) coordination at its His111 site
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-10-15T13:29:34Z
dc.identifier.eissn
1477-9234
dc.journal.volume
47
dc.journal.number
28
dc.journal.pagination
9274-9282
dc.journal.pais
Reino Unido
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dc.description.fil
Fil: Sánchez López, Carolina. Centro de Investigación y de Estudios Avanzados; México
dc.description.fil
Fil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina
dc.description.fil
Fil: Quintanar, Liliana. Centro de Investigación y de Estudios Avanzados; México
dc.journal.title
Dalton Transactions
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1039/C7DT03400H
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://pubs.rsc.org/en/content/articlelanding/2018/DT/C7DT03400H
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