Linked Life Data

20938536

Source:http://linkedlifedata.com/resource/pubmed/id/20938536

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
44
pubmed:dateCreated
2010-11-4
pubmed:abstractText
Using experimental and computational methods we identified the effects of mutation on the structure and dynamics of the amyloidogenic peptide apoC-II(60-70), in monomeric and oligomeric states. Methionine (Met60) substitutions to hydrophilic Gln, hydrophobic Val, and methionine sulfoxide residues were investigated and the results compared with observations of fibril formation by the wild-type, Met60Gln, Met60Val, and oxidised Met60 (oxi-Met) apoC-II(60-70) peptides. ThT fluorescence measurements showed fibril formation by all peptides, however with different kinetics. The wild-type and Met60Val peptides formed fibrils fastest, while oxi-Met and Met60Gln peptides exhibited significantly longer lag phases. Molecular dynamics simulations showed that the mutated monomers exhibited structural features consistent with fibril-forming propensity, such as ?-hairpin conformation and a hydrophobic core. However, important differences to the wild-type were also noted, such as increased structural flexibility (oxi-Met and Met60Gln systems) and a broader distribution of the aromatic angle orientation, which could contribute to the different fibrillation kinetics observed in these peptides. Our results also showed that the critical nucleus size for fibril formation by apoC-II(60-70) may not be very large, since tetrameric oligomers in anti-parallel configuration were very stable within the 100 ns of simulations. The single-point mutations Met60Val and Met60Gln had no significant effect on the structural stability of the tetramer. The rate of fibril formation by apoC-II(60-70) peptides was generally much faster compared to longer apoC-II(56-76) peptides. Also, the effects of amino acid modifications on the kinetics of peptide fibril formation differ from the effects observed for apoC-II(56-76) and full-length apoC-II, suggesting that additional mechanisms are involved in fibril formation by mature apoC-II.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1463-9084
pubmed:author
pubmed:issnType
Electronic
pubmed:day
28
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14762-74
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Effects of mutation on the amyloidogenic propensity of apolipoprotein C-II(60-70) peptide.
pubmed:affiliation
Health Innovations Research Institute, School of Applied Sciences, RMIT University, Melbourne, VIC, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't