Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 496, Issue 2, Pages 132-139Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2010.02.011
Keywords
SR-BI; Selective uptake; Efflux; Hydrophobicity; Extracellular domain; Cholesteryl ester
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Funding
- National Institutes of Health [HL-58012]
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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, L140/1.142, 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. (C) 2010 Elsevier Inc. All rights reserved.
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