PCSK9 (D5K4S) Rabbit mAb #55728

The proprotein convertases (PCs) are enzymes that activate precursor proteins through proteolytic cleavage within the secretory pathway. PCs comprise several enzymes that are basic amino acid-specific proteinases (furin, PC1/3, PC2, PC4, PACE4, PC5/6, and PC7), as well as nonbasic amino acid convertases (S1P and PC9) (1). PCs have a common structure that includes an N-terminal signal peptide for secretory pathway targeting; a pro-domain that is thought to act as an intramolecular chaperone; a catalytic domain containing the active site; a P-domain that contributes to the overall folding of the enzyme by regulating stability, calcium-, and pH-dependence; and a C-terminal domain that interacts with the membrane (2). PCs act in a tissue- and substrate-specific fashion to generate an array of bioactive peptides and proteins from precursors, both in the brain and the periphery (3).
Mutations in the PCSK9 gene (encoding proprotein converts subtilisin/kexin type 9, PC9) have been found to cause autosomal-dominant hypercholesterolemia. PCSK9 was therefore demonstrated to be a key factor involved in lipoprotein metabolism (4). PCSK9 acts as a chaperone protein that binds the LDL receptor (LDLR) at the cell membrane and induces LDLR lysosomal degradation rather than recycling (5). PCSK9 inhibition has since been a new therapeutic strategy for the treatment of hypercholesterolemia (6).