Scavenger receptor class B Type I (SR-BI) assembles into detergent-sensitive dimers and tetramers.
High density lipoproteins (HDL) are protective against cardiovascular disease due to their important role in the reverse cholesterol transport (RCT) pathway. The selective transfer of cholesteryl ester (CE) from the HDL core to cells, the last step in RCT, is mediated by scavenger receptor class B type I (SR-BI). SR-BI is a heavily glycosylated cell surface receptor that is highly expressed in the liver, ovaries, testes and adrenal glands, where selective uptake of HDL-CE is most prevalent. Previous studies have shown that SR-BI oligomerizes with itself in steroidogenic tissues as well as in diverse cell lines. In the present study, we provide further evidence for the homo-oligomerization of SR-BI. We show by FPLC and blue native PAGE that SR-BI forms complexes whose sizes suggest the formation of monomers, dimers, and tetramers. Interestingly, homo-oligomerization occurs even with the absence of SR-BI's C-terminal cytoplasmic domain. Finally, we report that an inhibitor of SR-BI-mediated cholesterol transport, BLT-1, and mutations in the putative leucine zipper region of SR-BI have profound effects on SR-BI function, however, they do not affect receptor self-association. These observations indicate that SR-BI homo-oligomerization occurs even when the receptor is non-functional.
Sahoo
Daisy
D
Department of Pharmacological Sciences, University Medical Center, State University of New York at Stony Brook, Stony Brook, NY 11794-8651, USA. sahoo@pharm.sunysb.edu
Darlington
Yolanda F
YF
Pop
Diana
D
Williams
David L
DL
Connelly
Margery A
MA
D000818:Animals; D019556:COS Cells; D002499:Centrifugation, Density Gradient; D002522:Chlorocebus aethiops; D002853:Chromatography, Liquid; D006224:Cricetinae; D003412:Cricetulus; D003902:Detergents / Q000494:pharmacology*; D019281:Dimerization; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D051122:Scavenger Receptors, Class B / Q000737:chemistry* / Q000378:metabolism*
D003902:Detergents; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B