Lipoprotein-Associated Phospholipase A2 Interacts with Phospholipid Vesicles via a Surface-Disposed Hydrophobic 伪-Helix

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• 作者：Jian Cao ; Yuan-Hao Hsu ; Sheng Li ; Virgil L. Woods ; Jr. ; Edward A. Dennis
• 刊名：Biochemistry
• 出版年：2011
• 出版时间：June 14, 2011
• 年：2011
• 卷：50
• 期：23
• 页码：5314-5321
• 全文大小：986K
• 年卷期：v.50,no.23(June 14, 2011)
• ISSN：1520-4995

文摘

Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) plays important roles in both the inhibition and promotion of inflammation in human disease. It catalyzes the hydrolytic inactivation of plasma platelet activating factor (PAF) and is also known as PAF acetylhydrolase. High levels of PAF are implicated in a variety of inflammatory diseases such as asthma, necrotizing enterocolitis, and sepsis. Lp-PLA₂ also associates with lipoproteins in human plasma where it hydrolyzes oxidized phospholipids to produce pro-inflammatory lipid mediators that can promote inflammation and the development of atherosclerosis. Lp-PLA₂ plasma levels have recently been identified as a biomarker of vascular inflammation, atherosclerotic vulnerability, and future cardiovascular events. The enzyme is thus a prominent target for the development of inflammation and atherosclerosis-modulating therapeutics. While the crystallographically determined structure of the enzyme is known, the enzyme鈥檚 mechanism of interaction with PAF and the function-modulating lipids in lipoproteins is unknown. We have employed peptide amide hydrogen鈥揹euterium exchange mass spectrometry (DXMS) to characterize the association of Lp-PLA₂ with dimyristoylphosphatidylcholine (DMPC) vesicles and found that specific residues 113鈥?20 in one of the enzyme鈥檚 surface-disposed hydrophobic 伪-helices likely mediate liposome binding.