title: The lysine-binding function of Lp(a).
abstract: The atherogenicity of Lp(a) is attributable to the binding of its apolipoprotein(a) component to fibrin and other plasminogen substrates. It can attenuate the activation of plasminogen, diminishing plasmin-dependent fibrinolysis and transforming growth factor-beta activation. Apolipoprotein(a) contains a major lysine-binding site in one of its kringle domains. Destroying this site by site-directed mutagenesis greatly reduces the binding of apolipoprotein(a) to lysine and fibrin. Transgenic mice expressing wild-type apolipoprotein(a) have a 5-fold increase in the development of lipid lesions, as well as a large increase in the focal deposition of apolipoprotein(a) in the aorta, compared to the lysine-binding site mutant strain and to non-transgenic litter mates. Although the adaptive function of apolipoprotein(a) remains obscure, a gene with similar structure has evolved by independent remodeling of the plasminogen twice during the course of mammalian evolution.
authors.affiliation: Falk Cardiovascular Research Center, Stanford University School of Medicine, CA 94305-5246, USA.
authors.forename: N W
authors.initials: NW
authors.lastname: Boonmark
authors.forename: R M
authors.initials: RM
authors.lastname: Lawn
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D001054:Apolipoproteins A / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D004195:Disease Models, Animal; D019143:Evolution, Molecular; D005246:Feedback / Q000502:physiology; D006364:Hedgehogs; D006801:Humans; D018082:Kringles / Q000502:physiology; D008055:Lipids / Q000032:analysis; D017270:Lipoprotein(a) / Q000235:genetics / Q000502:physiology*; D008239:Lysine / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D010958:Plasminogen / Q000235:genetics; D011485:Protein Binding / Q000502:physiology; D017385:Sequence Homology
chemical_list: D001054:Apolipoproteins A; D008055:Lipids; D017270:Lipoprotein(a); D010958:Plasminogen; D008239:Lysine