Premium
The lysine‐binding function of Lp(a)
Author(s) -
Boonmark Nataya W.,
Lawn Richard M.
Publication year - 1997
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.1997.tb04353.x
Subject(s) - plasmin , apolipoprotein b , lysine , fibrinolysis , lipoprotein(a) , mutant , chemistry , biochemistry , plasminogen activator , fibrin , binding site , microbiology and biotechnology , biology , gene , genetics , medicine , amino acid , immunology , enzyme , cholesterol
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‐β 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.