Journal article
Domain-induced activation of human phospholipase A2 type IIA: Local versus global lipid composition
Secretory human phospholipase A(2) type IIA (PLA(2)-IIA) catalyzes the hydrolysis of the sn-2 ester bond in glycerolipids to produce fatty acids and lysolipids. The enzyme is coupled to the inflammatory response, and its specificity toward anionic membrane interfaces suggests a role as a bactericidal agent.
PLA(2)-IIA may also target perturbed native cell membranes that expose anionic lipids to the extracellular face. However, anionic lipid contents in native cells appear lower than the threshold levels necessary for activation. By using phosphatidylcholine/phosphatidylglycerol model systems, we show that local enrichment of anionic lipids into fluid domains triggers PLA(2)-IIA activity.
In addition, the compositional range of enzyme activity is shown to be related to the underlying lipid phase diagram. A comparison is done between PLA(2)-IIA and snake venom PLA(2), which in contrast to PLA(2)-IIA hydrolyzes both anionic and zwitterionic membranes. In general, this work shows that PLA(2)-IIA activation can be accomplished through local enrichment of anionic lipids into domains, indicating a mechanism for PLA(2)-IIA to target perturbed native membranes with low global anionic lipid contents.
The results also show that the underlying lipid phase diagram, which determines the lipid composition at a local level, can be used to predict PLA(2)-IIA activity.
Language: | English |
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Publisher: | Biophysical Society |
Year: | 2006 |
Pages: | 3165-3175 |
ISSN: | 15420086 , 00063495 and 05236800 |
Types: | Journal article |
DOI: | 10.1529/biophysj.105.070987 |
ORCIDs: | 0000-0002-4258-8960 and Peters, Günther H.j. |
Animals Calorimetry, Differential Scanning Fluoresceins Group II Phospholipases A2 Humans Lipid Metabolism Lipids Membrane Microdomains Phosphatidylcholines Phosphatidylglycerols Phospholipases A Phospholipases A2 Protein Structure, Tertiary Snake Venoms Snakes dimyristoylphosphatidylglycerol fluorexon