Figure 2.

Human PCSK9 loss-of-function mutants have weaker interactions with CAP1 than the wild type. (A) The single-nucleotide variants of PCSK9-CRD reported to be associated with plasma LDL cholesterol levels in humans. (B) The loss-of-function PCSK9 mutants S668R and G679E lose their binding affinity to CAP1. CAP1-Myc and either wild-type PCSK9-Flag or each point mutant of PCSK9-Flag were overexpressed in HEK293 cells. Immunoprecipitation with Flag and immunoblotting with Myc (upper two figures of immunoblot), or immunoprecipitation with Myc and immunoblotting with Flag (immunoblot on the third and fourth lines). The level of PCSK9 in the culture media (the lowest line).