Identification of a Domain That Mediates Association of Platelet-activating Factor Acetylhydrolase with High Density Lipoprotein

The plasma form of platelet-activating factor (PAF) acetylhydrolase (PAF-AH), also known as lipoprotein-associated phospholipase A2 (Lp-PLA2) inactivates potent lipid messengers such as PAF and modified phospholipids generated in settings of oxidant stress. In humans, PAF-AH circulates in blood in f...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2008-06, Vol.283 (25), p.17099-17106
Main Authors: Gardner, Alison A., Reichert, Ethan C., Topham, Matthew K., Stafforini, Diana M.
Format: Article
Language:English
Subjects:
1-Alkyl-2-acetylglycerophosphocholine Esterase - metabolism
Amino Acid Sequence
Animals
Catalysis
Conserved Sequence
Humans
Lipoproteins - chemistry
Lipoproteins, HDL - chemistry
Lipoproteins, HDL - metabolism
Mice
Models, Biological
Molecular Sequence Data
Protein Binding
Protein Structure, Tertiary
Sequence Homology, Amino Acid
Substrate Specificity
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The plasma form of platelet-activating factor (PAF) acetylhydrolase (PAF-AH), also known as lipoprotein-associated phospholipase A2 (Lp-PLA2) inactivates potent lipid messengers such as PAF and modified phospholipids generated in settings of oxidant stress. In humans, PAF-AH circulates in blood in fully active form and associates with high and low density lipoproteins (HDL and LDL). Several studies suggest that the location of PAF-AH affects both the catalytic efficiency and the function of the enzyme in vivo. The distribution of PAF-AH among lipoproteins varies widely among mammals. Here, we report that mouse and human PAF-AHs associate with human HDL particles of different density. We made use of this observation in the development of a binding assay to identify domains required for association of human PAF-AH with human HDL. Sequence comparisons among species combined with domain-swapping and site-directed mutagenesis studies led us to the identification of C-terminal residues necessary for the association of human PAF-AH with human HDL. Interestingly, the region identified is not conserved among PAF-AHs, suggesting that PAF-AH interacts with HDL particles in a manner that is unique to each species. These findings contribute to our understanding of the mechanisms responsible for association of human PAF-AH with HDL and may facilitate future studies aimed at precisely determining the function of PAF-AH in each lipoprotein particle.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M802394200