A quantitative analysis of apolipoprotein binding to SR-BI: multiple binding sites for lipid-free and lipid-associated apolipoproteins.

Academic Article

Abstract

  • Competitive binding experiments were performed using Y1-BS1 adrenal cells to provide information about the interaction of HDL apolipoproteins with scavenger receptor class B, type I (SR-BI). Exchangeable apolipoproteins apolipoprotein A-I (apoA-I), apoA-II, apoE-2, apoE-3, and apoE-4 as phospholipid complexes bind like HDL3 to SR-BI via their multiple amphipathic alpha-helices; the concentrations required to reduce the binding of HDL3 to SR-BI by 50% (IC50) were similar and in the range of 35-50 microgram protein/ml. In the case of apoA-I, peptides corresponding to segments 1-85, 44-65, 44-87, 149-243, and 209-241 all had the same IC50 as each other (P = 0.86), showing that a specific amino acid sequence in apoA-I is not responsible for the interaction with SR-BI. The distribution of charged residues in the amphipathic alpha-helix affects the interaction, with class A and Y helices binding better than class G* helices. Synthetic alpha-helical peptides composed of either l or d amino acids can bind equally to the receptor. Association with phospholipid increases the amount of apolipoprotein binding to SR-BI without altering the affinity of binding. Lipid-free apolipoproteins compete only partially with the binding of HDL to SR-BI, whereas lipidated apolipoproteins compete fully. These results are consistent with the existence of more than one type of apolipoprotein binding site on SR-BI.
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    Keywords

  • Animals, Apolipoproteins, Binding, Competitive, CD36 Antigens, Cells, Cultured, Cholesterol Esters, Humans, Iodine Radioisotopes, Kinetics, Lipid Metabolism, Lipoproteins, HDL, Membrane Proteins, Phospholipids, Protein Binding, Protein Structure, Secondary, Receptors, Immunologic, Receptors, Lipoprotein, Receptors, Scavenger, Scavenger Receptors, Class A, Scavenger Receptors, Class B
  • Digital Object Identifier (doi)

    Author List

  • Thuahnai ST; Lund-Katz S; Anantharamaiah GM; Williams DL; Phillips MC
  • Start Page

  • 1132
  • End Page

  • 1142
  • Volume

  • 44
  • Issue

  • 6