Apolipoprotein(a)-Apolipoprotein B-100 assembly interface (Lp(a) assembly interface)

The Lipoprotein(a) [Lp(a)] assembly pathway/apoB interface is the biochemical site where apolipoprotein(a) [apo(a)] non-covalently binds to apolipoprotein B-100 [apoB-100] on the surface of low-density lipoprotein (LDL)-like particles to form Lp(a). This assembly process is a critical step in the production of Lp(a), a genetically determined lipoprotein that is structurally similar to LDL but contains the unique apo(a) protein (Tsimikas, 2017). Elevated plasma levels of Lp(a) are strongly associated with an increased risk of atherosclerotic cardiovascular disease, including myocardial infarction and stroke, as well as calcific aortic valve stenosis (Nissen et al., 2023). The interface is a high-value therapeutic target because Lp(a) levels are largely resistant to traditional lipid-lowering drugs like statins. Therapeutic interventions include small molecules like Muvalaplin, which directly disrupt the non-covalent binding at the apoB interface, and RNA-based therapies like Pelacarsen and Olpasiran that inhibit the synthesis of apo(a) to prevent assembly (O'Donoghue et al., 2022). By blocking this interface or reducing the availability of its components, these drugs aim to lower circulating Lp(a) and reduce cardiovascular risk.

Other names

apo(a)-apoB-100 interfaceLipoprotein(a) formation complexapoB-100 lysine binding siteLp(a) assembly pathway

Inhibition of the non-covalent interaction between apolipoprotein(a) and apolipoprotein B-100; antisense or siRNA-mediated knockdown of apolipoprotein(a) mRNA to prevent particle assembly.