C-terminal domain of apolipoprotein CII as both activator and competitive inhibitor of lipoprotein lipase.

In this study we have prepared peptides of the C-terminal domain of apolipoprotein CII (ApoCII) by a solid-peptide-synthesis technique and demonstrated that the C-terminal tetrapeptide, Lys-Gly-Glu-Glu, represents an inhibitor of lipoprotein lipase. The tetrapeptide not only inhibits the basal activity of lipoprotein lipase, but also blocks the activation effect of native ApoCII. The lengthening of this tetrapeptide resulted in a corresponding increase in affinity for lipoprotein lipase. This suggested that amino acids other than those of the C-terminal tetrapeptide also contribute to the binding affinity of ApoCII for lipoprotein lipase. On the basis of an essential requirement of the ApoCII terminal domain for binding to lipoprotein lipase, we suggest that the initial interaction of ApoCII, mediated via the C-terminal tetrapeptide, promotes the proper alignment of ApoCII with lipoprotein lipase, followed by the weak interaction of the ApoCII activator domain with the lipoprotein lipase activator site, enhancing the lipolysis process.