ELECTRON-MICROSCOPIC AND HYDRODYNAMIC CHARACTERIZATION OF RECOMBINANTAPOLIPOPROTEIN(A) AND ITS ASSOCIATION WITH LDL

A recombinant apo(a) containing 17 kringle 4 domains as well as the kr ingle 5 and protease domains of apo(a) was characterized by hydrodynam ic studies and electron microscopy. Recombinant apo(a) is a monomer in solution with a molecular weight of 325000 by sedimentation equilibri um and 320000 by sedimentation and diffusion, and it is a highly asymm etric molecule with a frictional ratio of 2.2. In the electron microsc ope recombinant apo(a) is visualized as a flexible chain of domains ap proximately 800 Angstrom long. Sedimentation velocity studies also dem onstrate that when it is mixed with LDL, recombinant apo(a) reversibly forms an Lp(a)-like complex with a 1:1 stoichiometry; moreover, compl ex formation is inhibited by 6-amino hexanoic acid. Hydrodynamic model ing and electron microscopy suggest that only a small portion of the r -apo(a) molecule interacts with the LDL and the rest of the chain exte nds into solution. Preliminary studies indicate that recombinant apo(a ) also binds mouse LDL.