Role of an intramolecular contact on lipoprotein uptake by the LDL receptor.

ABSTRACT: The LDL receptor (LDLR) is an endocytic receptor that plays a major role in the clearance of atherogenic lipoproteins from the circulation. During the endocytic process, the LDLR first binds lipoprotein at the cell surface and then traffics to endosomes, where the receptor releases bound lipoprotein. Release is acid-dependent and correlates with the formation of an intramolecular contact within the receptor. Human mutations at residues that form the contact are associated with familial hypercholesterolemia (FH) and the goal of the present study was to determine the role of contact residues on LDLR function. We show that mutations at nine contact residues reduce the ability of the LDLR to support lipoprotein uptake. Unexpectedly, only four of the mutations (W515A, W541A, H562Y and H586Y) im

SUBMITTER: Zhao Z 

PROVIDER: S-EPMC3092732 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature