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Insights into PCSK9-LDLR Regulation and Trafficking via the Differential Functions of MHC-I Proteins HFE and HLA-C

Cells. 2024-05; 
Sepideh Mikaeeli, Ali Ben Djoudi Ouadda, Alexandra Evagelidis, Rachid Essalmani, Oscar Henrique Pereira Ramos, Carole Fruchart-Gaillard, Nabil G Seidah
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Mutant Libraries … Human complementary DNAs (cDNAs) encoding wild-type and mutant forms of LDLR, PCSK9, HFE, and HLA-C (HFE and HLA-C WT cDNA purchased from Genscript) were generated … Get A Quote

摘要

PCSK9 is implicated in familial hypercholesterolemia via targeting the cell surface PCSK9-LDLR complex toward lysosomal degradation. The M2 repeat in the PCSK9's C-terminal domain is essential for its extracellular function, potentially through its interaction with an unidentified "protein X". The M2 repeat was recently shown to bind an R-x-E motif in MHC-class-I proteins (implicated in the immune system), like HLA-C, and causing their lysosomal degradation. These findings suggested a new role of PCSK9 in the immune system and that HLA-like proteins could be "protein X" candidates. However, the participation of each member of the MHC-I protein family in this process and their regulation of PCSK9's function have... More

关键词

HFE, HLA-C, LDLR, MHC-I, PCSK9, lipid metabolism