The structure of lipoprotein(a) and ligand-induced conformational changes

Lipoprotein(a) is composed of low-density lipoprotein linked both covalentl y and noncovalently to apolipoprotein(a). The structure of lipoprotein(a) a nd the interactions between low-density lipoprotein and apolipoprotein(a) w ere investigated by electron microscopy and correlated with analytical ultr acentrifugation. Electron microscopy of rotary-shadowed and unidirectionall y shadowed lipoprotein(a) prepared without glycerol revealed that it is a n early spherical particle with no large projections. After extraction of bot h lipoprotein(a) and low-density lipoprotein with glycerol prior to rotary shadowing, the protein components were observed to consist of a ring of den sity made up of nodules of different sizes. with apolipoprotein(a) and apol ipoprotein B-100 closely associated with each other. However, when lipoprot ein(a) was treated with a lysine analogue, 6-aminohexanoic acid, much of th e apolipoprotein(a) separated from the apolipoprotein B-100. In 6-aminohexa noic acid-treated preparations without glycerol extraction, lipoprotein(a) particles had an irregular mass of density around the core. In contrast, li poprotein(a) particles treated with 6-aminohexanoic acid in the presence of glycerol had a long tail, in which individual kringles could be distinguis hed, extending from the ring of apolipoprotein B-100. The length of the tai l was dependent on the particular isoform of apolipoprotein(a). Dissociatio n of the noncovalent interactions between apolipoprotein(a) and low-density lipoprotein as a result of shear forces or changes in the microenvironment may contribute to selective retention of lipoprotein(a) in the vasculature .