Linked Life Data

7907586

Source:http://linkedlifedata.com/resource/pubmed/id/7907586

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1994-4-18
pubmed:abstractText
Prion-related encephalopathies are characterized by cerebral accumulation of a post-translationally modified form of the cellular prion protein (PrPC), designated PrPSc. Evidence suggests that the conversion from PrPC to PrPSc involves changes in the secondary structure leading to an increase in beta-sheet content. We have previously shown that a synthetic peptide homologous to residues 106-126 of human PrP, belonging to a predicted alpha-helical domain, exhibits a beta-sheet conformation, forms amyloid-like fibrils, and is neurotoxic in vitro. The present study investigated how different chemicophysical conditions such as pH and ionic strength or a membrane-like environment influenced the secondary structure of this peptide. PrP 106-126 exhibited a predominantly beta-sheet structure in 200 mM phosphate buffer, pH 5.0, but a combination of beta-sheet and random coil structure in 200 mM phosphate buffer, pH 7.0, or in deionized water. The addition of trifluoroethanol (50% final concentration) to solutions of peptide in deionized water induced the appearance of an alpha-helical secondary structure, but did not modify the beta-sheet conformation of the peptide dissolved in 200 mM phosphate buffer, pH 5.0. In the presence of micelles formed by a 5% solution of sodium dodecyl sulfate, PrP 106-126 showed a high content of alpha-helix. When the peptide was dissolved in 5 mM phosphate buffer, pH 7.4, and incubated with liposomes, it changed from a prevalently random coil structure to a beta-sheet conformation. The environment-dependent conformational polymorphism of PrP 106-126 and its marked tendency to form stable beta-sheet structures at acidic pH could account for the shift from alpha-helix to beta-sheet associated with the conversion of PrPC to PrPSc, which occurs most likely in the endosomal-lysosomal compartment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7859-62
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Conformational polymorphism of the amyloidogenic and neurotoxic peptide homologous to residues 106-126 of the prion protein.
pubmed:affiliation
Istituto di Richerche Farmacologiche Mario Negri, Milan, Italy.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't