Interaction between the ligand-binding domain of the LDL receptor and the C-terminal domain of PCSK9 is required for PCSK9 to remain bound to the LDL receptor during endosomal acidification

• DOI: 10.1093/hmg/ddr578
• Publication Date: 2011-12-09T04:31:53Z
• Authors: K. Tveten; O. L. Holla; J. Cameron; T. B. Strom; K. E. Berge; J. K. Laerdahl; T. P. Leren
• Keywords: PCSK9; Proprotein Convertases; Kexin

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the epidermal growth factor homology domain repeat A of low-density lipoprotein receptor (LDLR) at cell surface and disrupts recycling internalized LDLR. As a consequence, LDLR is rerouted lysosomes for degradation. Although PCSK9 may bind an lacking ligand-binding domain, least three repeats are required reroute lysosomes. In this study, we have studied binding with or without increasingly acidic conditions in order mimic milieu LDLR:PCSK9 complex as it translocates from membrane sorting endosomes. These studies shown that rapidly released pH range 6.9–6.1. similar pattern release was also observed normal mutant C-terminal domain. Together these data indicate interaction between negatively charged positively remain bound during early phase endosomal acidification endosome.