The linkage with apolipoprotein (a) in lipoprotein (a) modifies the immunochemical and functional properties of apolipoprotein B.
Lipoprotein (a) [Lp(a)] was isolated from several donors and its apolipoprotein (a) [apo(a)] dissociated by a reductive treatment, generating the apo(a)-free form of Lp(a) [Lp(a--)] that contains apolipoprotein B (apo B) as its sole protein. Using anti-apo B monoclonal antibodies, the properties of apo B in Lp(a), Lp(a--), and autologous low-density lipoprotein (LDL) were compared. Marked differences in apo B immunoreactivity were found between these lipoproteins, due to the presence of apo(a) in Lp(a). Apo(a) enhanced the expression of two epitopes in the amino-terminal part of apo B while it diminished the immunoreactivity of three other epitopes in the LDL receptor binding domain. Accordingly, the binding of the lipoproteins to the LDL receptor was also decreased in the presence of apo(a). In a different experimental system, the incubation of antibodies that react with 27 distinct epitopes distributed along the whole length of apo B sequence with plastic-bound Lp(a) and Lp(a--) failed to reveal any epitope of apo B that is sterically hindered by the presence of apo(a). Our results demonstrate that the presence of apo(a) modified the organization and function of apo B in Lp(a) particles. The data presented indicate that most likely the modification is not due to a steric hindrance but that some more profound conformational changes are involved. We suggest that the formation of the disulfide bridge between apo B and apo(a) in Lp(a) alters the system of disulfide bonds present in apo B and thereby modifies apo B structure.
Zawadzki
Z
Z
Laboratory of Lipoprotein Metabolism, Clinical Research Institute of Montreal, Quebec, Canada.
Tercé
F
F
Seman
L J
LJ
Theolis
R T
RT
Breckenridge
W C
WC
Milne
R W
RW
Marcel
Y L
YL
D000911:Antibodies, Monoclonal; D001054:Apolipoproteins A / Q000276:immunology* / Q000378:metabolism; D001055:Apolipoproteins B / Q000276:immunology* / Q000378:metabolism; D001667:Binding, Competitive; D002478:Cells, Cultured; D000939:Epitopes; D006801:Humans; D007120:Immunochemistry; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000276:immunology* / Q000378:metabolism; D015394:Molecular Structure; D011973:Receptors, LDL / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001054:Apolipoproteins A; D001055:Apolipoproteins B; D000939:Epitopes; D017270:Lipoprotein(a); D008074:Lipoproteins; D011973:Receptors, LDL