The binding of animal low-density lipoproteins to human apolipoprotein(a).
Lipoprotein(a) [Lp(a)] is a risk factor for coronary artery disease. It is composed of lipids and apolipoprotein(a) [apo(a)] linked to apolipoprotein B (apoB) by a disulphide bond between Cys-4057 of apo(a)'s kringle 36 and possibly Cys-3734 of apoB. We call this the covalent apo(a): apoB-Lp interaction, to distinguish it from the non-covalent apo(a)/Lp(a): apoB-Lp interaction, which is probably mediated by apo(a)'s kringle 33 and residues 3304-3317 of apoB. The non-covalent interaction could be the initial interaction which brings apo(a) and apoB together prior to covalent linkage and Lp(a) formation. The non-covalent apo(a)/Lp(a)-binding site on apoB is evolutionarily more ancient than the covalent apo(a)-binding site on apoB. Both human and non-human low-density lipoproteins (LDLs) bind non-covalently to human apo(a)/Lp(a); however, only rabbit and human LDLs bind covalently to human apo(a). The non-covalent interaction between mouse LDL and human apo(a)/Lp(a) has a Kd of (1.7 +/- 1.33) x 10(-7) M (n = 3). This explains the co-localization of human apo(a) and mouse apoB in the atherosclerotic lesions of human apo(a) transgenic mice and supports our hypothesis that the non-covalent interaction is a contributing factor to apo(a) atherogenicity.
Trieu
V N
VN
Department of Medicine, University of North Texas Health Science Center, Fort Worth 76107, USA.
McConathy
W J
WJ
D000818:Animals; D001053:Apolipoproteins / Q000235:genetics / Q000378:metabolism*; D053241:Apoprotein(a); D016466:CHO Cells; D002478:Cells, Cultured; D002645:Chickens; D003001:Cloning, Molecular; D006224:Cricetinae; D006801:Humans; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011485:Protein Binding; D011817:Rabbits; D013045:Species Specificity
D001053:Apolipoproteins; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D053241:Apoprotein(a)