Proprotein convertase subtilisin kexin type 9 (PCSK9) has been shown to be involved in the regulation of extracellular levels of the low-density lipoprotien receptor (LDLR). Although PCSK9 is a subtilase, it has not been shown to degrade the LDLR, and its LDLR-lowering mechanism remains uncertain. Here we report the crystal structure of human PCSK9 at 2.3 Å resolution. PCSK9 has subtilisin-like pro- and catalytic domains, and the stable interaction between these domains prevents access to PCSK9's catalytic site. The C-terminal domain of PCSK9 has a novel protein fold and may mediate protein-protein interactions. The structure of PCSK9 provides insight into its biochemical characteristics and biological function. © 2007 Elsevier Ltd. All rights reserved.
Piper, D. E., Jackson, S., Liu, Q., Romanow, W. G., Shetterly, S., Thibault, S. T., … Walker, N. P. C. (2007). The Crystal Structure of PCSK9: A Regulator of Plasma LDL-Cholesterol. Structure, 15(5), 545–552. https://doi.org/10.1016/j.str.2007.04.004