NMR Structure of the C-Terminal Transmembrane Domain of the HDL Receptor, SR-BI, and a Functionally Relevant Leucine Zipper Motif

Structure. 2017 Mar 7;25(3):446-457. doi: 10.1016/j.str.2017.01.001. Epub 2017 Feb 2.


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 complex facilitates delivery of cholesterol into cells and is likely mediated by receptor dimerization. This work describes the use of nuclear magnetic resonance (NMR) spectroscopy to generate the first high-resolution structure of the C-terminal transmembrane domain of SR-BI. This region of SR-BI harbors a leucine zipper dimerization motif, which when mutated impairs the ability of the receptor to bind HDL and mediate cholesterol delivery. These losses in function correlate with the inability of SR-BI to form dimers. We also identify juxtamembrane regions of the extracellular domain of SR-BI that may interact with the lipid surface to facilitate cholesterol transport functions of the receptor.

Keywords: NMR; SR-BI; cholesterol; detergent micelle; dimerization; high density lipoprotein; juxtamembrane; leucine zipper; selective uptake; transmembrane domain.

MeSH terms

  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Humans
  • Leucine Zippers
  • Lipoproteins, HDL / metabolism*
  • Magnetic Resonance Spectroscopy
  • Mice
  • Models, Molecular
  • Mutagenesis, Site-Directed*
  • Protein Structure, Secondary
  • Scavenger Receptors, Class B / chemistry*
  • Scavenger Receptors, Class B / genetics*
  • Scavenger Receptors, Class B / metabolism


  • Lipoproteins, HDL
  • Scarb1 protein, mouse
  • Scavenger Receptors, Class B