Journal article
Helical domains that mediate lipid solubilization and ABCA1-specific cholesterol efflux in apolipoproteins C-I and A-II
Journal of lipid research, Vol.54(7), pp.1939-1948
07/01/2013
DOI: 10.1194/jlr.M037903
PMCID: PMC3679395
PMID: 23620136
Abstract
Many of the apolipoproteins in HDL can elicit cholesterol efflux via ABCA1, a critical initial step in HDL formation. Recent work has indicated that omnipresent amphipathic helices play a critical role, and these have been studied intensively in the most common HDL protein, apolipoprotein (apo)A-I. However, little information exists about helical domain arrangement in other apolipoproteins. We studied two of the smallest apolipoproteins known to interact with ABCA1, human apoA-II and apoC-I, in terms of ability to reorganize phospholipid (PL) bilayers and to promote ABCA1-mediated cholesterol. We found that both proteins contained helical domains that were fast and slow with respect to solubilizing PL. ABCA1-medated efflux required a minimum of a bihelical polypeptide comprised of at least one each of a slow and fast lipid reorganizing domain. In both proteins, the fast helix was located at the C terminus preceded by a slow helix. Helical placement in apoC-I was not critical for ABCA1 activity, but helix swaps in apoA-II dramatically disrupted cholesterol efflux, indicating that the tertiary structure of the longer apolipoprotein is important for the pathway. This work has implications for a more complete molecular understanding of apolipoprotein-mediated cholesterol efflux.
Details
- Title: Subtitle
- Helical domains that mediate lipid solubilization and ABCA1-specific cholesterol efflux in apolipoproteins C-I and A-II
- Creators
- Loren E. Smith - University of CincinnatiJere P. Segrest - University of Alabama at BirminghamW. Sean Davidson - University of Alabama at Birmingham
- Resource Type
- Journal article
- Publication Details
- Journal of lipid research, Vol.54(7), pp.1939-1948
- DOI
- 10.1194/jlr.M037903
- PMID
- 23620136
- PMCID
- PMC3679395
- NLM abbreviation
- J Lipid Res
- ISSN
- 0022-2275
- eISSN
- 1539-7262
- Publisher
- Elsevier
- Number of pages
- 10
- Grant note
- R01 HL-67093 / National Institutes of Health Grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA American Heart Association
- Language
- English
- Date published
- 07/01/2013
- Academic Unit
- Anesthesia
- Record Identifier
- 9984949239302771
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