Linked Life Data

15708851

Source:http://linkedlifedata.com/resource/pubmed/id/15708851

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2005-4-11
pubmed:abstractText
Apolipoprotein E (apoE) is a 34-kDa resident of lipoproteins that plays a key role in cholesterol homeostasis in plasma and in brain. It is composed of an N-terminal (NT) domain (residues 1-191) and a C-terminal (CT) domain (residues 201-299). Of the three major isoforms (apoE2, -E3, and -E4), apoE4 is considered a risk factor for both cardiovascular and Alzheimer disease. Compared with apoE3, domain interaction between NT and CT domains is believed to direct the lipoprotein distribution preference of apoE4 for very low density lipoprotein-sized particles. We examined the relative disposition of apoE4 NT and CT domains in lipid-free and lipid-bound forms by monitoring pyrene excimer fluorescence emission as a direct indicator of spatial proximity. Site-specific labeling of apoE4 by N-(1-pyrene)maleimide was accomplished after substitution of Cys residues for Arg-61 in NT domain and Glu-255 in CT domain. Pyrene labeling did not alter the lipoprotein distribution pattern of apoE4 in plasma. Pyrene excimer fluorescence was noted in lipid-free pyrene-R61C/E255C/apoE4 in mixtures containing excess wild-type apoE4, which was attributed to intramolecular spatial proximity between these specified sites. Upon disruption of tertiary interaction, a large decrease in excimer fluorescence emission was noted in pyrene-R61C/E255C/apoE4. In dimyristoylphosphatidylcholine/pyrene-R61C/E255C/apoE4 discoidal complexes, pyrene excimer fluorescence emission was retained. Taken together with fluorescence quenching and cross-linking analysis, a looped-back model of apoE4 is proposed in lipid-bound state, including spherical lipoprotein particles, wherein residues Arg-61 and Glu-255 are proximal to one another.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14605-10
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15708851-Apolipoprotein E4, pubmed-meshheading:15708851-Apolipoproteins E, pubmed-meshheading:15708851-Arginine, pubmed-meshheading:15708851-Cross-Linking Reagents, pubmed-meshheading:15708851-Cysteine, pubmed-meshheading:15708851-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:15708851-Fluorescence Resonance Energy Transfer, pubmed-meshheading:15708851-Glutamic Acid, pubmed-meshheading:15708851-Humans, pubmed-meshheading:15708851-Lipids, pubmed-meshheading:15708851-Lipoproteins, pubmed-meshheading:15708851-Models, Molecular, pubmed-meshheading:15708851-Mutagenesis, Site-Directed, pubmed-meshheading:15708851-Protein Binding, pubmed-meshheading:15708851-Protein Conformation, pubmed-meshheading:15708851-Protein Isoforms, pubmed-meshheading:15708851-Protein Structure, Tertiary, pubmed-meshheading:15708851-Pyrenes, pubmed-meshheading:15708851-Risk Factors, pubmed-meshheading:15708851-Spectrometry, Fluorescence
pubmed:year
2005
pubmed:articleTitle
Examination of lipid-bound conformation of apolipoprotein E4 by pyrene excimer fluorescence.
pubmed:affiliation
Lipid Biology in Health and Disease Research Group, Children's Hospital Oakland Research Institute, Oakland, California 94609, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't