FIGURE 1.

PCSK9 domains and protease cleavage sites. A, cartoon indicating the three main PCSK9 domains: the prodomain, catalytic (Cat), and C-terminal (CT) domains. The N-segment (Ser¹⁵³–Arg²¹⁸) comprises the N-terminal portion of the catalytic domain up to the furin cleavage site residue Arg²¹⁸. The molecular masses determined by MS (see Fig. 5) are indicated for the N-segment, ΔN-Cat_CT, and Cat_CT. B, the 218 loop comprising the P4-P4′ amino acid sequence according to the Schechter and Berger nomenclature (29). The primary cleavage site for furin and hepsin (Arg²¹⁸-Gln²¹⁹) is indicated by a solid arrow, and the secondary cleavage site that is specific for hepsin (Arg²¹⁵-Phe²¹⁶) is indicated by a dashed arrow.