Negatively Cooperative Binding of High-Density Lipoprotein to the

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Biochemistry 2011, 50, 1818–1830 DOI: 10.1021/bi101657j

Negatively Cooperative Binding of High-Density Lipoprotein to the HDL Receptor SR-BI† Thomas J. F. Nieland,‡,§ Shangzhe Xu,‡ Marsha Penman,‡ and Monty Krieger*,‡ ‡

Department of Biology, Massachusetts Institute of Technology, Room 68-483, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States, and §Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, Massachusetts 02142, United States Received October 14, 2010; Revised Manuscript Received January 9, 2011 ABSTRACT: Scavenger receptor class B, type I (SR-BI), is a high-density lipoprotein (HDL) receptor, which also binds low-density lipoprotein (LDL), and mediates the cellular selective uptake of cholesteryl esters from lipoproteins. SR-BI also is a coreceptor for hepatitis C virus and a signaling receptor that regulates cell metabolism. Many investigators have reported that lipoproteins bind to SR-BI via a single class of independent (not interacting), high-affinity binding sites (one site model). We have reinvestigated the ligand concentration dependence of 125I-HDL binding to SR-BI and SR-BI-mediated specific uptake of [3H]CE from [3H]CE-HDL using an expanded range of ligand concentrations (