Apolipoprotein(a)-Apolipoprotein B-100 interaction (Apo(a)-ApoB-100 interaction)

The Apolipoprotein(a)-Apolipoprotein B-100 interaction is the critical biochemical step in the formation of Lipoprotein(a) [Lp(a)], a plasma lipoprotein that is a major independent risk factor for cardiovascular disease [Tsimikas, 2017, JACC]. This process occurs primarily in hepatocytes and involves a two-step mechanism: an initial non-covalent binding between the Kringle IV domains (specifically types 7 and 8) of Apolipoprotein(a) and the Apolipoprotein B-100 component of Low-Density Lipoprotein (LDL), followed by the formation of a stabilizing covalent disulfide bond [Koschinsky & Marcovina, 2004, Curr Opin Lipidol]. Elevated levels of Lp(a) are associated with increased risks of myocardial infarction, stroke, and aortic stenosis due to its pro-atherogenic and pro-thrombotic properties [Schmidt et al., 2016, J Lipid Res]. Unlike other lipid-lowering targets, Lp(a) levels are largely determined by genetics and are resistant to traditional statin therapy. Novel therapeutic agents, such as the small molecule Muvalaplin, are designed to specifically inhibit this protein-protein interaction, effectively lowering plasma Lp(a) concentrations by preventing its assembly [Nicholls et al., 2023, JAMA].

Other names

Lipoprotein(a) assemblyApolipoprotein(a)-LDL bindingApo(a)-ApoB-100 complex formationCovalent attachment of Apolipoprotein(a) to Apolipoprotein B-100

Inhibition of the non-covalent precursor binding between the Kringle IV domains (specifically KIV7-KIV8) of Apolipoprotein(a) and the Apolipoprotein B-100 component of LDL, preventing the subsequent formation of the covalent disulfide bond [Nicholls et al., 2023, JAMA].