title: The crystal structure of PCSK9: a regulator of plasma LDL-cholesterol.
abstract: 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 A 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.
authors.affiliation: Department of Molecular Structure, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, California 94080, USA.
authors.forename: Derek E
authors.initials: DE
authors.lastname: Piper
authors.forename: Simon
authors.initials: S
authors.lastname: Jackson
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: William G
authors.initials: WG
authors.lastname: Romanow
authors.forename: Susan
authors.initials: S
authors.lastname: Shetterly
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Thibault
authors.forename: Bei
authors.initials: B
authors.lastname: Shan
authors.forename: Nigel P C
authors.initials: NP
authors.lastname: Walker
mesh_terms: D008078:Cholesterol, LDL / Q000037:antagonists & inhibitors / Q000097:blood*; D018360:Crystallography, X-Ray; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry / Q000502:physiology; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D017510:Protein Folding; D025941:Protein Interaction Mapping; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000502:physiology*
chemical_list: D008078:Cholesterol, LDL; D010446:Peptide Fragments; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases