title: Low-density lipoprotein activates the protease region of recombinant apo(a).
abstract: The interaction of recombinant apo(a) (r-apo(a)) with low-density lipoprotein (LDL) has been examined using ultracentrifugation and affinity chromatography. R-apo(a) forms a non-covalent complex with human LDL. This LDL-r-apo(a) complex, reconstituted Lp(a), r-Lp(a), which can be isolated by ultracentrifugation, has protease activity. The protease activity reached maximum at an equimolar ratio of r-apo(a) and LDL. Proline and epsilon aminocaproic acid (at a concentration of 50 mM) caused dissociation of r-Lp(a) and simultaneous loss of enzyme activity. Mouse LDL that did not form a complex with r-apo(a) did not activate the protease region of r-apo(a). Unlike plasma Lp(a), r-Lp(a) was dissociated during affinity chromatography on Lysine-Sepharose. This dissociation led to loss of enzyme activity. We conclude that the formation of a non-covalent complex between r-apo(a) and LDL leads to activation of the protease region of r-apo(a). The results suggest that non-covalent binding between r-apo(a) and LDL is a pre-requisite for the enzyme activity of the protease region of r-apo(a).
authors.affiliation: National Public Health Institute, Department of Biochemistry, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Pursiainen
authors.forename: M
authors.initials: M
authors.lastname: Jauhiainen
authors.forename: C
authors.initials: C
authors.lastname: Ehnholm
mesh_terms: D000818:Animals; D001054:Apolipoproteins A / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D051379:Mice; D011994:Recombinant Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology
chemical_list: D001054:Apolipoproteins A; D008077:Lipoproteins, LDL; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases