LIPID-BINDING OF APOLIPOPROTEIN CII IS REQUIRED FOR STIMULATION OF LIPOPROTEIN-LIPASE ACTIVITY AGAINST APOLIPOPROTEIN CII-DEFICIENT CHYLOMICRONS

Human apolipoprotein CII (apo CII) consists of 79 amino acid residues. The amino-terminal two thirds of the molecule binds to lipid through the formation of amphipathic helixes, while the carboxy-terminal third is engaged in activation of lipoprotein lipase (LPL). On the basis of studies in model systems, it was previously concluded that fragments of apo CII spanning residues 51-79 were sufficient for activation, alt hough they do not bind to lipid. In the present study, we used chylomi crons from an apo CII-deficient patient to reinvestigate this possibil ity, with a physiologically relevant substrate. Human LPL expressed ve ry low activity against these chylomicrons. Addition of apo CII caused an immediate >100-fold increase in lipase activity. The apo CII fragm ent 50-79 caused very little stimulation, though with some synthetic l ipid substrates, this fragment was fully effective. LPL bound to the c hylomicrons even in the absence of apo CII but apparently in a nonprod uctive manner. In accord with this finding, the main effect of apo CII was on the V-MAX for the reaction, with little or no change in the ap parent K-M. We conclude that the lipid-binding part of apo CII is need ed for activity of LPL against chylomicrons. This idea is in accord wi th previous studies with lipid monolayers, which showed that the lipid -binding part is necessary for activation of the enzyme at high surfac e pressures.