The Multifaceted Biology of PCSK9.

ABSTRACT: This article reviews the discovery of PCSK9, its structure-function characteristics, and its presently known and proposed novel biological functions. The major critical function of PCSK9 deduced from human and mouse studies, as well as cellular and structural analyses, is its role in increasing the levels of circulating low-density lipoprotein (LDL)-cholesterol (LDLc), via its ability to enhance the sorting and escort of the cell surface LDL receptor (LDLR) to lysosomes. This implicates the binding of the catalytic domain of PCSK9 to the EGF-A domain of the LDLR. This also requires the presence of the C-terminal Cys/His-rich domain, its binding to the secreted cytosolic cyclase associated protein 1, and possibly another membrane-bound "protein X". Curiously, in PCSK9-deficient mice, an alt

SUBMITTER: Seidah NG 

PROVIDER: S-EPMC9113161 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature