Abstract

According to the CDC, 1 in 3 adults in the US has high cholesterol, which is linked to cardiovascular disease. Cholesterol, a hydrophobic molecule, is transported in the blood by binding a lipoprotein. Scavenger receptor class B type 1 (SR‐B1), a transmembrane protein that binds high density lipoprotein (HDL) carrying cholesterol, helps transfer cholesterol from HDL into liver cells where it can be excreted in bile. This is important for lowering blood cholesterol levels and reducing the risk of heart disease and stroke. SR‐B1 belongs to a larger family of scavenger receptor proteins that includes lysosome membrane protein 2 (LIMP‐2), and SR‐B1 and LIMP‐2 share structural homology. The structure of the C‐terminal transmembrane domain of SR‐B1, determined through NMR, is composed of three helices with a leucine zipper motif. Mutagenesis studies implicate this leucine zipper motif in dimerization of SR‐B1 and proper receptor function. A crystal structure of LIMP‐2 revealed the existence of a large, primarily hydrophobic cavity that runs the entire length of the protein that suggests a role in the selective transfer of cholesterol into the liver cell. Using 3D printing technology, the Cedarburg SMART (Students Modeling A Research Topic) Team utilized the known structure of LIMP‐2 to investigate structure‐function relationships in SR‐B1. Determining important HDL/SR‐B1 interactions will increase knowledge of how SR‐B1 functions in transferring cholesterol from plasma HDL to the liver for excretion and can lead to the development of medical treatments to increase cholesterol excretion by the liver and prevent heart disease and stroke.Support or Funding InformationThe MSOE Center for BioMolecular Modeling would like to acknowledge and thank the National Institutes of Health Science Education Partnership Award (NIH‐SEPA 1R25OD010505‐01) and the National Institutes of Health Clinical and Translational Science Award (NIH‐CTSA UL1RR031973) for their support in funding the 2017–2018 SMART Team Team program.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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