LIGAND-INDUCED CONFORMATIONAL CHANGE OF LIPOPROTEIN(A)

Lipoprotein(a) undergoes a dramatic, reversible conformational change on binding 6-aminohexanoic acid (6-AHA), as measured by a decrease in the sedimentation rate, the magnitude of which is directly proportional to apo(a) mass. A similar reversible transition from a compact to an extended form has been shown to occur in plasminogen on occupation of a weak lysine binding site. The magnitude of the change in Lp(a) with large apo(a) is about 2.5 times that seen for plasminogen, however. Regardless of apo(a) size, binding analysis indicated that 1.4−4 molecules of 6-AHA bound per Lp(a) particle; the midpoint of the conformational change occurs at 6-AHA concentrations of 100−200 mM. Since rhesus Lp(a), which lacks both kringle V and the strong lysine binding site on kringle IV 10, also undergoes a similar conformational change, the phenomenon may be attributable to weak sites, possibly located in K-IV 5−8. Compact Lp(a), i.e., native Lp(a), had a frictional ratio (f/fo) of 1.2 that was independent of apo(a) ma...