[HTML][HTML] Loss-and gain-of-function PCSK9 variants: cleavage specificity, dominant negative effects, and low density lipoprotein receptor (LDLR) degradation
S Benjannet, J Hamelin, M Chrétien… - Journal of Biological …, 2012 - ASBMB
The proprotein convertase PCSK9 is a major target in the treatment of hypercholesterolemia
because of its ability bind the LDL receptor (LDLR) and enhance its degradation in
endosomes/lysosomes. In the endoplasmic reticulum, the zymogen pro-PCSK9 is first
autocatalytically cleaved at its internal Gln 152↓, resulting in a secreted enzymatically
inactive complex of PCSK9 with its inhibitory prosegment (prosegment· PCSK9), which is the
active form of PCSK9 on the LDLR. We mutagenized the P1 cleavage site Gln 152 into all …
because of its ability bind the LDL receptor (LDLR) and enhance its degradation in
endosomes/lysosomes. In the endoplasmic reticulum, the zymogen pro-PCSK9 is first
autocatalytically cleaved at its internal Gln 152↓, resulting in a secreted enzymatically
inactive complex of PCSK9 with its inhibitory prosegment (prosegment· PCSK9), which is the
active form of PCSK9 on the LDLR. We mutagenized the P1 cleavage site Gln 152 into all …
