HDL and scavenger receptors: A love-hate relationship

The interaction of high density lipoprotein (HDL) with its receptor, scavenger receptor BI (SR-BI) is critical for lowering plasma cholesterol levels and reducing the risk for cardiovascular disease. The HDL/SR-BI interaction facilitates delivery of cholesterol into cells and is likely mediated by receptor dimerization. Today’s seminar will describe: (1) the importance of cholesterol clearance from the body via proper SR-BI/HDL interactions; (2) the use of nuclear magnetic resonance techniques (NMR) to generate the first high-resolution structure of the C-terminal transmembrane domain of SR-BI, a region that harbors a leucine zipper dimerization motif, that when mutated, impairs the ability of SR-BI to bind HDL and mediate cholesterol delivery; and (3) how oxidized forms of HDL are dysfunctional and promote cardiovascular disease through interactions with the scavenger receptor, CD36.