Linked Life Data

20104925

Source:http://linkedlifedata.com/resource/pubmed/id/20104925

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-2-11
pubmed:abstractText
Recent experimental data demonstrate that small, soluble amyloid-beta42 oligomers play an important role in Alzheimer's disease because they exhibit neurotoxic properties and also act as seed for fibril growth. We performed all-atom molecular dynamics simulations in explicit solvent of 0.7 micros in total on five Abeta9-42 oligomers (monomer through pentamer) starting from the fibril conformation. The initial conformation proves to be stable in the trimer to pentamer, and the two parallel in-register beta-sheets as well as the connecting turn are preserved. The dimer undergoes larger conformational changes in its C-terminus, and the predominant conformation detected exhibits an additional antiparallel beta-sheet in one of the subunits. This conformational rearrangement allows efficient shielding of hydrophobic residues from the solvent, which is not possible for a dimer in the fibril conformation. In addition to the presence of the hydrogen bonds in the beta-sheets, the larger oligomers are stabilized by interchain D23-K28 salt bridges, whereas a D23-N27 interaction is found in the dimer. The degree of structural similarity to the fibril conformation detected for the oligomers in the simulation may also offer a structural explanation for the experimental finding that trimers and tetramers act as more potent seeds in fibril formation than dimers because only small conformational changes will be required for fibril growth. The fact that the dimer predominantly exists in conformations distinct from the larger oligomers and the fibril is also interesting for the design of anti-Alzheimer drugs, because it suggests that multiple drugs might be required to target the structurally different neurotoxic oligomers.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1520-5207
pubmed:author
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
114
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2219-26
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Amyloid-beta42 oligomer structures from fibrils: a systematic molecular dynamics study.
pubmed:affiliation
Bioinformatik, Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't