DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lim, Kwang Hun | - |
dc.contributor.author | Kim, Yun Kyung | - |
dc.contributor.author | Chang, Young-Tae | - |
dc.date.accessioned | 2018-06-15T05:14:32Z | - |
dc.date.available | 2018-06-15T05:14:32Z | - |
dc.date.created | 2017-09-08 | - |
dc.date.issued | 2007-11 | - |
dc.identifier.issn | 0006-2960 | - |
dc.identifier.uri | https://oasis.postech.ac.kr/handle/2014.oak/50251 | - |
dc.description.abstract | Transition-metal ions (Cu(2+) and Zn(2+)) play critical roles in the A beta plaque formation. However, precise roles of the metal ions in the A beta amyloidogenesis have been controversial. In this study, the molecular mechanism of the metal-induced A beta oligomerization was investigated with extensive metal ion titration NMR experiments. Upon additions of the metal ions, the N-terminal region (1-16) of the A beta (1-40) peptide was selectively perturbed. In particular, polar residues 4-8 and 13-15 were more strongly affected by the metal ions, suggesting that those regions may be the major binding sites of the metal ions. The NMR signal changes of the N-terminal region were dependent on the peptide concentrations (higher peptide concentrations resulted in stronger signal changes), suggesting that the metal ions facilitate the intermolecular contact between the A beta peptides. The A beta (1-40) peptides (> 30 mu M) were eventually oligomerized even at low temperature (3 degrees C), where the A beta peptides are stable as monomeric forms without the metal ions. The real-time oligomerization process was monitored by (1)H/(15)N HSQC NMR experiments, which provided the first residue-specific structural transition information. Hydrophobic residues 12-21 initially underwent conformational changes due to the intermolecular interactions. After the initial structural rearrangements, the C-terminal residues (32-40) readjusted their conformations presumably for effective oligomerization. Similar structural changes of the metal-free A beta (1-40) peptides were also observed in the presence of the preformed oligomers, suggesting that the conformational transitions may be the general molecular mechanism of the A beta (1-40) amyloidogenesis. | - |
dc.language | English | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.relation.isPartOf | BIOCHEMISTRY | - |
dc.subject | AMYLOID-BETA | - |
dc.subject | ALZHEIMERS-DISEASE | - |
dc.subject | COPPER-BINDING | - |
dc.subject | IN-VITRO | - |
dc.subject | EXPERIMENTAL CONSTRAINTS | - |
dc.subject | PROTEIN OLIGOMERIZATION | - |
dc.subject | CU(II) POTENTIATION | - |
dc.subject | INDUCED AGGREGATION | - |
dc.subject | SECONDARY STRUCTURE | - |
dc.subject | HYDROGEN-PEROXIDE | - |
dc.title | Investigations of the molecular mechanism of metal-induced A beta (1-40) amyloidogenesis | - |
dc.type | Article | - |
dc.identifier.doi | 10.1021/bi701112z | - |
dc.type.rims | ART | - |
dc.identifier.bibliographicCitation | BIOCHEMISTRY, v.46, no.47, pp.13523 - 13532 | - |
dc.identifier.wosid | 000251150000006 | - |
dc.date.tcdate | 2019-02-01 | - |
dc.citation.endPage | 13532 | - |
dc.citation.number | 47 | - |
dc.citation.startPage | 13523 | - |
dc.citation.title | BIOCHEMISTRY | - |
dc.citation.volume | 46 | - |
dc.contributor.affiliatedAuthor | Chang, Young-Tae | - |
dc.identifier.scopusid | 2-s2.0-36749100841 | - |
dc.description.journalClass | 1 | - |
dc.description.journalClass | 1 | - |
dc.description.wostc | 48 | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | AMYLOID-BETA | - |
dc.subject.keywordPlus | ALZHEIMERS-DISEASE | - |
dc.subject.keywordPlus | COPPER-BINDING | - |
dc.subject.keywordPlus | IN-VITRO | - |
dc.subject.keywordPlus | EXPERIMENTAL CONSTRAINTS | - |
dc.subject.keywordPlus | PROTEIN OLIGOMERIZATION | - |
dc.subject.keywordPlus | CU(II) POTENTIATION | - |
dc.subject.keywordPlus | INDUCED AGGREGATION | - |
dc.subject.keywordPlus | SECONDARY STRUCTURE | - |
dc.subject.keywordPlus | HYDROGEN-PEROXIDE | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
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