Project B02.2

Scavenger receptor class B type 1 (SR-B1), a member of the CD36 superfamily, is an integral transmembrane glycoprotein containing an N- and C-terminal transmembrane region framing a glycosylated extracellular ectodomain. SR-B1 plays a central role in lipid metabolism, mediating the selective uptake of cholesteryl esters from high-density lipoproteins (HDL) in steroidogenic tissues and the liver [1]. Beyond its role in lipid transport, SR-B1 also serves as a cellular entry factor for Hepatitis C Virus (HCV) [2].

SR-B1 is believed to exert its cholesterol transfer activity via oligomerization within the membrane, and homodimers and higher oligomers have been described. However, how oligomerization is involved in the cholesterol transfer activity and the precise mechanism underlying the key role of SR-B1 in cholesterol transport remains elusive to date. Our aim is to gain mechanistic insights into SR-B1-mediated cholesterol transfer by employing in vitro reconstitution of intact SR-B1 combined with fluorescence-labeled cholesterol transfer assays together with structural biology approaches.