Extracellular hydrophobic regions in scavenger receptor BI play a key role in mediating HDL-cholesterol transport. Arch Biochem Biophys 2010 Apr 15;496(2):132-9
Date
03/12/2010Pubmed ID
20219439Pubmed Central ID
PMC2853188DOI
10.1016/j.abb.2010.02.011Scopus ID
2-s2.0-77951023562 (requires institutional sign-in at Scopus site) 30 CitationsAbstract
The binding of high density lipoprotein (HDL) to scavenger receptor BI (SR-BI) is responsible for whole-body cholesterol disposal via reverse cholesterol transport. The extracellular domain of SR-BI is required for HDL binding and selective uptake of HDL-cholesterol. We identified six highly hydrophobic regions in this domain that may be important for receptor activity and performed site-directed mutagenesis to investigate the importance of these regions in SR-BI-mediated cholesterol transport. Non-conservative mutation of the regions encompassing V67, L140/L142, V164 or V221 reduced hydrophobicity and impaired the ability of SR-BI to bind HDL, mediate selective uptake of HDL-cholesterol, promote cholesterol efflux, and enlarge the cholesterol oxidase-sensitive pool of membrane free cholesterol. In contrast, conservative mutations at V67, V164 or V221 did not affect the hydrophobicity or these cholesterol transport activities. We conclude that the hydrophobicity of N-terminal extracellular regions of SR-BI is critical for cholesterol transport, possibly by mediating receptor-ligand and/or receptor-membrane interactions.
Author List
Papale GA, Nicholson K, Hanson PJ, Pavlovic M, Drover VA, Sahoo DAuthor
Daisy Sahoo PhD Dean, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBiological Transport, Active
COS Cells
Cholesterol, HDL
Extracellular Fluid
Hydrophobic and Hydrophilic Interactions
Scavenger Receptors, Class B
Signal Transduction
