Linked Life Data

10727238

Source:http://linkedlifedata.com/resource/pubmed/id/10727238

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2000-5-4
pubmed:abstractText
Apolipoprotein C-II (apoC-II) is an exchangeable plasma apolipoprotein and an endogenous activator of lipoprotein lipase (LpL). Genetic deficiencies of apoC-II and overexpression of apoC-II in transgenic mice are both associated with severe hyperlipidemia, indicating a complex role for apoC-II in the regulation of blood lipid levels. ApoC-II exerts no effect on the activity of LpL for soluble substrates, suggesting that activation occurs via the formation of a lipid-bound complex. We have synthesized a peptide corresponding to amino acid residues 39-62 of mature human apoC-II. This peptide does not bind to model lipid surfaces but retains the ability to activate LpL. Conjugation of the fluorophore 7-nitrobenz-2-oxa-1,3-diazole (NBD) to the N-terminal alpha-amino group of apoC-II39-62 facilitated determination of the affinity of the peptide for LpL using fluorescence anisotropy measurements. The dissociation constant describing this interaction was 0.23 microM, and was unchanged when LpL was lipid-bound. Competitive binding studies showed that apoC-II39-62 and full-length apoC-II exhibited the same affinity for LpL in aqueous solution, whereas the affinity for full-length apoC-II was increased at least 1 order of magnitude in the presence of lipid. We suggest that while the binding of apoC-II to the lipid surface promotes the formation of a high-affinity complex of apoC-II and LpL, activation occurs via direct helix-helix interactions between apoC-II39-62 and the loop covering the active site of LpL.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3433-40
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10727238-Amino Acid Sequence, pubmed-meshheading:10727238-Animals, pubmed-meshheading:10727238-Apolipoprotein C-II, pubmed-meshheading:10727238-Apolipoproteins C, pubmed-meshheading:10727238-Binding, Competitive, pubmed-meshheading:10727238-Cattle, pubmed-meshheading:10727238-Circular Dichroism, pubmed-meshheading:10727238-Dimyristoylphosphatidylcholine, pubmed-meshheading:10727238-Enzyme Activation, pubmed-meshheading:10727238-Humans, pubmed-meshheading:10727238-Lipase, pubmed-meshheading:10727238-Lipid Bilayers, pubmed-meshheading:10727238-Lipid Metabolism, pubmed-meshheading:10727238-Lipids, pubmed-meshheading:10727238-Lipoprotein Lipase, pubmed-meshheading:10727238-Molecular Sequence Data, pubmed-meshheading:10727238-Peptide Fragments, pubmed-meshheading:10727238-Phospholipases, pubmed-meshheading:10727238-Protein Binding, pubmed-meshheading:10727238-Recombinant Proteins, pubmed-meshheading:10727238-Solutions
pubmed:year
2000
pubmed:articleTitle
Apolipoprotein C-II39-62 activates lipoprotein lipase by direct lipid-independent binding.
pubmed:affiliation
Russell Grimwade School of Biochemistry and Molecular Biology, University of Melbourne, Parkville 3052, Victoria, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't