Linked Life Data

8909295

Source:http://linkedlifedata.com/resource/pubmed/id/8909295

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
44
pubmed:dateCreated
1996-12-13
pubmed:abstractText
In this paper, we test the hypothesis that peptide models of a highly conserved domain of apolipoprotein E (amino acids 41-60 in human apo E) modulate the binding and internalization of LDL to cell surface receptors in a conformationally specific manner. Three peptides were compared: peptide I containing the natural sequence of amino acids 41-60 of human apo E; peptide III containing side-chain lactam cross-links designed to enhance alpha-helical structure; and peptide II containing cross-links designed to prevent formation of alpha-helices. Peptide III was shown previously to consist of two short alpha-helical domains linked by a turn and to have more alpha-helical content than peptide I, while peptide II was shown to have less helical content than either peptide III or I(Luo et al., 1994). Peptide III induced a 30-fold increase in the specific binding of 125I-LDL to normal human skin fibroblasts and a 60-fold increase in the binding to fibroblasts lacking the LDL-R. This same peptide also restored the binding to normal fibroblasts of 125I-LDL from a patient with familial defective apolipoprotein B, the R3500-->Q mutation. Analysis of binding indicated an increase in the apparent number of binding sites, with little effect on the affinity of 125I-LDL for the cell surface. Heparinase treatment of the cells did not abrogate this effect, suggesting that the increased binding is not mediated by cell surface glycans. LDL internalization but not degradation was also increased by peptide III. Similar but smaller effects were also induced by peptide I. Peptide II was much less active than peptide I or III. Thus, the order of biological activity was the same as the order of alpha-helical content, i.e., peptide III > peptide I > peptide II. These results suggest a hitherto unknown biological function for a highly conserved domain of apolipoprotein E, and this bioactivity was shown by peptide models to be specific to the alpha-helical conformation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13975-84
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:8909295-Amino Acid Sequence, pubmed-meshheading:8909295-Animals, pubmed-meshheading:8909295-Apolipoproteins E, pubmed-meshheading:8909295-Binding, Competitive, pubmed-meshheading:8909295-Binding Sites, pubmed-meshheading:8909295-Cell Line, pubmed-meshheading:8909295-Cell Membrane, pubmed-meshheading:8909295-Conserved Sequence, pubmed-meshheading:8909295-Heparin Lyase, pubmed-meshheading:8909295-Humans, pubmed-meshheading:8909295-Lipoproteins, LDL, pubmed-meshheading:8909295-Liver, pubmed-meshheading:8909295-Models, Molecular, pubmed-meshheading:8909295-Molecular Sequence Data, pubmed-meshheading:8909295-Peptide Fragments, pubmed-meshheading:8909295-Polysaccharide-Lyases, pubmed-meshheading:8909295-Protein Binding, pubmed-meshheading:8909295-Protein Conformation, pubmed-meshheading:8909295-Rats, pubmed-meshheading:8909295-Receptors, LDL
pubmed:year
1996
pubmed:articleTitle
Conformationally specific enhancement of receptor-mediated LDL binding and internalization by peptide models of a conserved anionic N-terminal domain of human apolipoprotein E.
pubmed:affiliation
Department of Biochemistry, University of Chicago, Illinois 60637, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't