Polymorphic forms of Lp(a) with different structural and functional properties: cold-induced self-association and binding to fibrin and lysine-Sepharose.
Two different Lp(a) polymorphs were isolated from the same individual and shown to have important differences both in their solution properties and in interaction with lysine Sepharose and fibrin. One Lp(a) particle (d-Lp(a)) with a large apo(a) isoform had a density of 1.087 g/ml and a molecular weight of 3.17 million, while the other Lp(a) particle with a small apo(a) isoform having a mobility faster than that of apoB was larger and had a molecular weight of 3.75 million and a density of 1.054 g/ml. D-Lp(a) underwent cold-induced self-association and also had a higher affinity for lysine Sepharose, whereas the other Lp(a) polymorph did not. Both Lp(a) particles bound fibrin via two different binding sites, one of which involved fibrin lysine residues which are also recognized by plasminogen. Lysine-mediated binding of d-Lp(a) by fibrin was ten times stronger than that of the other Lp(a) particle, whereas non-lysine-mediated binding of either Lp(a) species by fibrin was of equal strength. At saturation, 80% of d-Lp(a) bound fibrin at sites that did not involve lysine residues, whereas only 33% of the other Lp(a) polymorph bound to these sites. These findings indicate that the binding of Lp(a) to fibrin is more complex than previously thought and imposes another layer of difficulty on our understanding of how Lp(a) regulates and/or impairs fibrinolysis.
Fless
G M
GM
Department of Medicine, University of Chicago, IL 60637.
Snyder
M L
ML
D015119:Aminocaproic Acid / Q000494:pharmacology; D003080:Cold Temperature; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D017270:Lipoprotein(a) / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D015394:Molecular Structure; D008970:Molecular Weight; D010958:Plasminogen / Q000378:metabolism; D011110:Polymorphism, Genetic; D011485:Protein Binding / Q000187:drug effects; D012685:Sepharose / Q000031:analogs & derivatives / Q000378:metabolism
D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; C030675:lysine-sepharose; D005337:Fibrin; D010958:Plasminogen; D012685:Sepharose; D015119:Aminocaproic Acid