Apolipoprotein A-II alters the proteome of human lipoproteins and enhances cholesterol efflux from ABCA1
- PMID: 28476857
- PMCID: PMC5496035
- DOI: 10.1194/jlr.M075382
Apolipoprotein A-II alters the proteome of human lipoproteins and enhances cholesterol efflux from ABCA1
Abstract
HDLs are a family of heterogeneous particles that vary in size, composition, and function. The structure of most HDLs is maintained by two scaffold proteins, apoA-I and apoA-II, but up to 95 other "accessory" proteins have been found associated with the particles. Recent evidence suggests that these accessory proteins are distributed across various subspecies and drive specific biological functions. Unfortunately, our understanding of the molecular composition of such subspecies is limited. To begin to address this issue, we separated human plasma and HDL isolated by ultracentrifugation (UC-HDL) into particles with apoA-I and no apoA-II (LpA-I) and those with both apoA-I and apoA-II (LpA-I/A-II). MS studies revealed distinct differences between the subfractions. LpA-I exhibited significantly more protein diversity than LpA-I/A-II when isolated directly from plasma. However, this difference was lost in UC-HDL. Most LpA-I/A-II accessory proteins were associated with lipid transport pathways, whereas those in LpA-I were associated with inflammatory response, hemostasis, immune response, metal ion binding, and protease inhibition. We found that the presence of apoA-II enhanced ABCA1-mediated efflux compared with LpA-I particles. This effect was independent of the accessory protein signature suggesting that apoA-II induces a structural change in apoA-I in HDLs.
Keywords: ATP binding cassette transporter A1; high density lipoprotein/structure; proteomics.
Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.
Conflict of interest statement
The authors state they have no conflict of interest with this article.
Figures
![Fig. 1.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5496035/bin/1374fig1.gif)
![Fig. 2.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5496035/bin/1374fig2.gif)
![Fig. 3.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5496035/bin/1374fig3.gif)
![Fig. 4.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5496035/bin/1374fig4.gif)
![Fig. 5.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5496035/bin/1374fig5.gif)
![Fig. 6.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5496035/bin/1374fig6.gif)
![Fig. 7.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5496035/bin/1374fig7.gif)
![Fig. 8.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5496035/bin/1374fig8.gif)
![Fig. 9.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5496035/bin/1374fig9.gif)
![Fig. 10.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5496035/bin/1374fig10.gif)
Similar articles
-
Structure-function relationships in reconstituted HDL: Focus on antioxidative activity and cholesterol efflux capacity.Biochim Biophys Acta Mol Cell Biol Lipids. 2017 Sep;1862(9):890-900. doi: 10.1016/j.bbalip.2017.05.010. Epub 2017 May 18. Biochim Biophys Acta Mol Cell Biol Lipids. 2017. PMID: 28529180
-
Influence of apolipoprotein A-I and apolipoprotein A-II availability on nascent HDL heterogeneity.J Lipid Res. 2013 Dec;54(12):3464-70. doi: 10.1194/jlr.M043109. Epub 2013 Oct 1. J Lipid Res. 2013. PMID: 24089247 Free PMC article.
-
Role of apoA-I, ABCA1, LCAT, and SR-BI in the biogenesis of HDL.J Mol Med (Berl). 2006 Apr;84(4):276-94. doi: 10.1007/s00109-005-0030-4. Epub 2006 Feb 25. J Mol Med (Berl). 2006. PMID: 16501936 Review.
-
ATP-binding cassette transporter AI and its role in HDL formation.Curr Opin Lipidol. 2005 Feb;16(1):19-25. doi: 10.1097/00041433-200502000-00005. Curr Opin Lipidol. 2005. PMID: 15650559 Review.
-
Molecular and cellular physiology of apolipoprotein A-I lipidation by the ATP-binding cassette transporter A1 (ABCA1).J Biol Chem. 2004 Feb 27;279(9):7384-94. doi: 10.1074/jbc.M306963200. Epub 2003 Dec 4. J Biol Chem. 2004. PMID: 14660648
Cited by
-
Closing the gaps in patient management of dyslipidemia: stepping into cardiovascular precision diagnostics with apolipoprotein profiling.Clin Proteomics. 2024 Mar 1;21(1):19. doi: 10.1186/s12014-024-09465-w. Clin Proteomics. 2024. PMID: 38429638 Free PMC article. Review.
-
A novel assay to measure low-density lipoproteins binding to proteoglycans.PLoS One. 2024 Jan 31;19(1):e0291632. doi: 10.1371/journal.pone.0291632. eCollection 2024. PLoS One. 2024. PMID: 38295021 Free PMC article.
-
Understanding HDL Metabolism and Biology Through In Vivo Tracer Kinetics.Arterioscler Thromb Vasc Biol. 2024 Jan;44(1):76-88. doi: 10.1161/ATVBAHA.123.319742. Epub 2023 Nov 30. Arterioscler Thromb Vasc Biol. 2024. PMID: 38031838 Review.
-
HDL Function across the Lifespan: From Childhood, to Pregnancy, to Old Age.Int J Mol Sci. 2023 Oct 18;24(20):15305. doi: 10.3390/ijms242015305. Int J Mol Sci. 2023. PMID: 37894984 Free PMC article. Review.
-
Human cerebrospinal fluid contains diverse lipoprotein subspecies enriched in proteins implicated in central nervous system health.Sci Adv. 2023 Sep;9(35):eadi5571. doi: 10.1126/sciadv.adi5571. Epub 2023 Aug 30. Sci Adv. 2023. PMID: 37647397 Free PMC article.
References
-
- Davidson W. S. 2017. Davidson Lab Webpage: Lipoprotein Proteome Watch. Accessed March 15, 2017, at www.DavidsonLab.com.
-
- Navab M., Hama S. Y., Anantharamaiah G. M., Hassan K., Hough G. P., Watson A. D., Reddy S. T., Sevanian A., Fonarow G. C., and Fogelman A. M.. 2000. Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: steps 2 and 3. J. Lipid Res. 41: 1495–1508. - PubMed
-
- Barter P. J., and Rye K. A.. 1996. High density lipoproteins and coronary heart disease. Atherosclerosis. 121: 1–12. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous