Association with lipids or detergents is essential for preservation of the active structure of lipoprotein-associated phospholipase A2

•The monomeric Lp-PLA2 is unstable due to the expose of hydrophobic interfacial binding region or substrate binding compartment to water milieu.•Association with lipoproteins or micelle of detergent, or formation of self-aggregate is necessary for Lp-PLA2 to maintain its native structure.•The method can be harnessed to detect the interaction between recombinant Lp-PLA2 and components of lipoprotein particles. Recombinant lipoprotein-associated phospholipase A2 (rLp-PLA2) expressed in HEK293 cells has a propensity to form oligomers in the absence of detergents. Dilution of rLp-PLA2 in the absence of detergents results in irreversible inactivation of the enzyme. The monomeric rLp-PLA2 may expose its hydrophobic interfacial binding region or substrate binding compartment to water and that may cause structural collapsing of the enzyme. Formation of self-aggregate, complex with binding partners or association with detergent micelles is to block the access of aqueous solvent to the hydrophobic substrate binding site and therefore prevents the structural collapsing. Dilution inactivation of the enzyme can be prevented in the presence of LDL or HDL suggesting that Lp-PLA2 association with lipoprotein particles (LDL and HDL) is necessary for Lp-PLA2 to maintain its enzymatic activity in human plasma. Formation of higher affinity complex gave better protection of rLp-PLA2 structure and activity. The method can be harnessed to detect the interaction between rLp-PLA2 and components of lipoprotein particles. Apo(a), ApoB 100 and ApoA1 were found to protect the enzyme from inactivation at roughly the similar level (˜80 ± 5%) comparing to human serum albumin control (˜40%). One mg/ml pig brain phospholipid showed 100% protection under the same conditions.