Phospholipid Binding and Self‐Association of the Major Apoprotein of Human and Baboon High‐Density Lipoproteins

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Abstract
The relationship between self-association and phospholipid binding of the human and the baboon apoA-I protein was investigated. The enthalpy changes on binding dimyristoyl lecithin and lysolecithin to either the human or the baboon native apoA-I protein were measured in a microcalorimeter. An endothermal process, most pronounced for the human apoprotein, was observed at low phospholipid levels. At higher phospholipid to protein ratios the binding was exothermal. Gel filtration experiments on Sephadex G-200 showed that the native apoprotein of both species consists of dimers and tetramers. The baboon native apoA-I protein contained a higher amount of dimers. After preincubation of the apoA-I protein with lysolecithin, the enthalpy changes measured on subsequent binding of dimyristoyl lecithin were shifted towards more exothermal values compared to the curve for the native apoprotein. The amplitude of this shift corresponds to that of the endothermal process observed on binding dimyristoyl lecithin to the native apoprotein. This process was attributed to a phospholipid-induced disaggregation of the apoA-I protein. Gel filtration data showed a decreased extent of aggregation in the apoA-I protein preincubated with lysolecithin. This sample consisted exclusively of dimers. Ultracentrifugal flotation of the complexes formed between the apoA-I protein, and, respectively, dimyristoyl lecithin and sphingomyelin indicated that preincubation with lysolecithin increased the extent of complex formation. The dimeric form of the apoA-I protein apparently possesses the highest affinity for phospholipids. Any dissociation of higher polymers enhances the phospholipid-binding capacity of the human and the baboon apoA-I protein.