[HTML][HTML] NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol
S Benjannet, D Rhainds, R Essalmani, J Mayne… - Journal of Biological …, 2004 - ASBMB
The discovery of autosomal dominant hypercholesterolemic patients with mutations in the
PCSK9 gene, encoding the proprotein convertase NARC-1, resulting in the missense
mutations suggested a role in low density lipoprotein (LDL) metabolism. We show that the
endoplasmic reticulum-localized proNARC-1 to NARC-1 zymogen conversion is Ca 2+-
independent and that within the zymogen autocatalytic processing site SSVFAQ↓ SIP Val at
P4 and Pro at P3′ are critical. The S127R and D374Y mutations result in∼ 50–60% and≥ …
PCSK9 gene, encoding the proprotein convertase NARC-1, resulting in the missense
mutations suggested a role in low density lipoprotein (LDL) metabolism. We show that the
endoplasmic reticulum-localized proNARC-1 to NARC-1 zymogen conversion is Ca 2+-
independent and that within the zymogen autocatalytic processing site SSVFAQ↓ SIP Val at
P4 and Pro at P3′ are critical. The S127R and D374Y mutations result in∼ 50–60% and≥ …