Linked Life Data

19995075

Source:http://linkedlifedata.com/resource/pubmed/id/19995075

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
49
pubmed:dateCreated
2009-12-9
pubmed:abstractText
Aggregation of Amyloid beta (Abeta) peptide has been linked to the neurodegenerative Alzheimer's Disease and implicated in other amyloid diseases including cerebral amyloid angiopathy. Abeta peptide is generated by cleavage of the amyloid precursor protein (APP) by transmembrane proteases. It is crucial to determine the structures of beta-amyloid peptides in a membrane to provide a molecular basis for the cleavage mechanism. We report the structures of amyloid beta peptide (Abeta(1-40) and Abeta(1-42)) as well as the 672-726 fragment of APP (referred to as Abeta(1-55)) in a membrane environment determined by replica-exchange molecular dynamics simulation. Abeta(1-40) is found to have two helical domains A (13-22) and B(30-35) and a type I beta-turn at 23-27. The peptide is localized at the interface between membrane and solvent. Substantial fluctuations in domain A are observed. The dominant simulated tertiary structure of Abeta(1-40) is observed to be similar to the simulated Abeta(1-42) structure. However, there are differences observed in the overall conformational ensemble, as characterized by the two-dimensional free energy surfaces. The fragment of APP (Abeta(1-55)) is observed to have a long transmembrane helix. The position of the transmembrane region and ensemble of membrane structures are elucidated. The conformational transition between the transmembrane Abeta(1-55) structure, prior to cleavage, and the Abeta(1-40) structure, following cleavage, is proposed.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1520-5126
pubmed:author
pubmed:issnType
Electronic
pubmed:day
16
pubmed:volume
131
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17843-52
pubmed:dateRevised
2010-12-17
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Structures of beta-amyloid peptide 1-40, 1-42, and 1-55-the 672-726 fragment of APP-in a membrane environment with implications for interactions with gamma-secretase.
pubmed:affiliation
Department of Chemistry, Boston University, Boston, Massachusetts 02215, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural