DC Field | Value | Language |
---|---|---|
dc.contributor.author | Atwood, Craig S. | ko |
dc.contributor.author | Scarpa, Richard C. | ko |
dc.contributor.author | Huang, Xudong | ko |
dc.contributor.author | Moir, Robert D. | ko |
dc.contributor.author | Jones, Walton D | ko |
dc.contributor.author | Fairlie, David P. | ko |
dc.contributor.author | Tanzi, Rudolph E. | ko |
dc.contributor.author | Bush, Ashley I. | ko |
dc.date.accessioned | 2013-02-27T15:12:12Z | - |
dc.date.available | 2013-02-27T15:12:12Z | - |
dc.date.created | 2012-02-06 | - |
dc.date.created | 2012-02-06 | - |
dc.date.issued | 2000-09 | - |
dc.identifier.citation | JOURNAL OF NEUROCHEMISTRY, v.75, no.3, pp.1219 - 1233 | - |
dc.identifier.issn | 0022-3042 | - |
dc.identifier.uri | http://hdl.handle.net/10203/69268 | - |
dc.description.abstract | Cu and Zn have been shown to accumulate in the brains of Alzheimer's disease patients. We have previously reported that Cu2+ and Zn2+ bind amyloid beta (A beta), explaining their enrichment in plaque pathology. Here we detail the stoichiometries and binding affinities of multiple cooperative Cu2+-binding sites on synthetic A beta 1-40 and A beta 1-42. We have developed a ligand displacement technique (competitive metal capture analysis) that uses metal-chelator complexes to evaluate metal ion binding to A beta, a notoriously self-aggregating peptide. This analysis indicated that there is a very-high-affinity Cu2+-binding site on A beta 1-42 (log K-app = 17.2) that mediates peptide precipitation and that the tendency of this peptide to self-aggregate in aqueous solutions is due to the presence of trace Cu2+ contamination (customarily similar to 0.1 mu M). In contrast, A beta 1-40 has much lower affinity for Cu2+ at this site (estimated log K-app = 10.3), explaining why this peptide is less self-aggregating. The greater Cu2+-binding affinity of A beta 1-42 compared with A beta 1-40 is associated with significantly diminished negative cooperativity, The role of trace metal contamination in inducing A beta precipitation was confirmed by the demonstration that A beta peptide (10 mu M) remained soluble for 5 days only in the presence of high-affinity Cu2+-selective chelators. | - |
dc.language | English | - |
dc.publisher | Wiley-Blackwell | - |
dc.subject | A-BETA | - |
dc.subject | CEREBROSPINAL-FLUID | - |
dc.subject | TRACE-ELEMENTS | - |
dc.subject | HYDROGEN-PEROXIDE | - |
dc.subject | SERUM ZINC | - |
dc.subject | DISEASE | - |
dc.subject | BRAIN | - |
dc.subject | PROTEIN | - |
dc.subject | AGGREGATION | - |
dc.subject | IMBALANCES | - |
dc.title | Characterization of copper interactions with Alzheimer amyloid beta peptides: Identification of an attomolar-affinity copper binding site on amyloid beta 1-42 | - |
dc.type | Article | - |
dc.identifier.wosid | 000088868500037 | - |
dc.identifier.scopusid | 2-s2.0-0033844944 | - |
dc.type.rims | ART | - |
dc.citation.volume | 75 | - |
dc.citation.issue | 3 | - |
dc.citation.beginningpage | 1219 | - |
dc.citation.endingpage | 1233 | - |
dc.citation.publicationname | JOURNAL OF NEUROCHEMISTRY | - |
dc.identifier.doi | 10.1046/j.1471-4159.2000.0751219.x | - |
dc.contributor.localauthor | Jones, Walton D | - |
dc.contributor.nonIdAuthor | Atwood, Craig S. | - |
dc.contributor.nonIdAuthor | Scarpa, Richard C. | - |
dc.contributor.nonIdAuthor | Huang, Xudong | - |
dc.contributor.nonIdAuthor | Moir, Robert D. | - |
dc.contributor.nonIdAuthor | Fairlie, David P. | - |
dc.contributor.nonIdAuthor | Tanzi, Rudolph E. | - |
dc.contributor.nonIdAuthor | Bush, Ashley I. | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | human amyloid beta peptide | - |
dc.subject.keywordAuthor | copper | - |
dc.subject.keywordAuthor | affinity | - |
dc.subject.keywordAuthor | stoichiometry | - |
dc.subject.keywordAuthor | Alzheimer&apos | - |
dc.subject.keywordAuthor | s disease | - |
dc.subject.keywordAuthor | binding affinity method | - |
dc.subject.keywordAuthor | chelators | - |
dc.subject.keywordPlus | A-BETA | - |
dc.subject.keywordPlus | CEREBROSPINAL-FLUID | - |
dc.subject.keywordPlus | TRACE-ELEMENTS | - |
dc.subject.keywordPlus | HYDROGEN-PEROXIDE | - |
dc.subject.keywordPlus | SERUM ZINC | - |
dc.subject.keywordPlus | DISEASE | - |
dc.subject.keywordPlus | BRAIN | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | AGGREGATION | - |
dc.subject.keywordPlus | IMBALANCES | - |
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