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NMR Structure of the C-Terminal Transmembrane Domain of the HDL Receptor, SR-BI, and a Functionally Relevant Leucine Zipper Motif. Structure 2017 03 07;25(3):446-457

Date

02/07/2017

Pubmed ID

28162952

Pubmed Central ID

PMC5575897

DOI

10.1016/j.str.2017.01.001

Scopus ID

2-s2.0-85011284406   3 Citations

Abstract

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.

Author List

Chadwick AC, Jensen DR, Hanson PJ, Lange PT, Proudfoot SC, Peterson FC, Volkman BF, Sahoo D

Authors

Francis C. Peterson PhD Professor in the Biochemistry department at Medical College of Wisconsin
Daisy Sahoo PhD Vice Chair, Professor in the Medicine department at Medical College of Wisconsin
Brian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
COS Cells
Humans
Leucine Zippers
Lipoproteins, HDL
Magnetic Resonance Spectroscopy
Mice
Models, Molecular
Mutagenesis, Site-Directed
Protein Structure, Secondary
Scavenger Receptors, Class B
jenkins-FCD Prod-444 eb4ebd1a08581aba961d3befd3b851a3c3ec6b46