Apolipoprotein(a)-Apolipoprotein B-100 protein-protein interface (Apo(a)-ApoB100 interface)

The Apolipoprotein(a)-Apolipoprotein B-100 (Apo(a)-ApoB100) protein-protein interface is the critical assembly site for the formation of Lipoprotein(a) [Lp(a)], a highly atherogenic and prothrombotic lipoprotein particle. Lp(a) consists of an LDL-like particle containing one molecule of Apolipoprotein B-100 (ApoB100) covalently linked to a single molecule of the highly polymorphic glycoprotein Apolipoprotein(a) [Apo(a)]. The assembly process begins with a non-covalent interaction between the lysine-binding sites in the kringle IV domains (specifically KIV-7 and KIV-8) of Apo(a) and specific lysine residues on the surface of ApoB100. This initial interaction is essential for the subsequent formation of the disulfide bridge between Cys4057 of Apo(a) and Cys4326 of ApoB100. Elevated levels of Lp(a) are a genetically determined, independent risk factor for cardiovascular diseases, including coronary artery disease, stroke, and calcific aortic valve stenosis. Traditional lipid-lowering therapies like statins have little to no effect on Lp(a) levels, making the assembly site an attractive therapeutic target. Small molecule inhibitors, such as Muvalaplin, are designed to bind to the lysine-binding sites of Apo(a), thereby disrupting the protein-protein interface and preventing the assembly of the Lp(a) particle.

Other names

Lipoprotein(a) assembly siteApolipoprotein(a)-Apolipoprotein B-100 complex assembly siteApo(a)-ApoB100 interaction siteLp(a) assembly site

Inhibition of the non-covalent protein-protein interaction between the lysine-binding sites of Apolipoprotein(a) and Apolipoprotein B-100, thereby preventing the assembly of Lipoprotein(a) particles.