Linked Life Data

19853305

Source:http://linkedlifedata.com/resource/pubmed/id/19853305

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2009-11-9
pubmed:abstractText
There is a large body of evidence that divalent metal ions, particularly copper, might play a role in several protein folding pathologies like Alzheimer's disease, Parkinson's disease or the prion diseases. However, contribution of metal ions on pathogenesis and their molecular influence on the formation of amyloid structures is not clear. Therefore, the general influence of metals on the formation of amyloids is still controversially discussed. We have utilized the well established system of yeast Sup35p-NM to investigate the role of three different metal ions, Cu(2+), Mn(2+) and Zn(2+), on amyloidogenesis. Recently, it has been shown that the prion determining region NM of the Saccharomyces cerevisiae prion protein Sup35p, which is responsible for the yeast prion phenotype [PSI(+)], specifically binds Cu(2+) ions. We further characterized the affinity of NM for Cu(2+), which were found to be comparable to that of other amyloidogenic proteins like the mammalian prion protein PrP. The specific binding sites could be located in the aminoterminal N-region which is known to initiate formation of amyloidogenic nuclei. In the presence of Cu(2+), fibril nucleation was significantly delayed, probably due to influences of copper on the oligomeric ensemble of soluble Sup35p-NM, since Cu(2+) altered the tertiary structure of soluble Sup35p-NM, while no influences on fibril elongation could be detected. The secondary structure of soluble or fibrous protein and the morphology of the fibrils were apparently not altered when assembled in presence of Cu(2+). In contrast, Mn(2+) and Zn(2+) did not bind to Sup35p-NM and did not exhibit significant effects on the formation of NM amyloid fibrils.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1873-3344
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1711-20
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Influence of divalent copper, manganese and zinc ions on fibril nucleation and elongation of the amyloid-like yeast prion determinant Sup35p-NM.
pubmed:affiliation
Lehrstuhl für Biomaterialien, Fakultät für Angewandte Naturwissenschaften, Universität Bayreuth, Universitätsstrasse 30, 95447 Bayreuth, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't