ArticleBiochimica et biophysica acta2012
Influence of C-terminal α-helix hydrophobicity and aromatic amino acid content on apolipoprotein A-I functionality.
Article in Biochimica et biophysica acta, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- ABCA1-Mediated Structural Diversity of HDL Subspecies and Their Proposed Roles in Cardioprotection.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Is ABCA1 a lipid transfer protein?Journal of lipid research · 2018Review
- Charged Residues in the C-Terminal Domain of Apolipoprotein A-I Modulate Oligomerization.Biochemistry · 2018Article
- Expression of the C-terminal domain of human apolipoprotein A-I using a chimeric apolipoprotein.Protein expression and purification · 2017Article
- Transfer of C-terminal residues of human apolipoprotein A-I to insect apolipophorin III creates a two-domain chimeric protein with enhanced lipid binding activity.Biochimica et biophysica acta. Biomembranes · 2017Article
- ApoA1 and ApoA1-specific self-antibodies in cardiovascular disease.Laboratory investigation; a journal of technical methods and pathology · 2016Review
- Lipid-free Apolipoprotein A-I Structure: Insights into HDL Formation and Atherosclerosis Development.Archives of medical research · 2015Review
- Apolipoprotein AI deficiency inhibits serum opacity factor activity against plasma high density lipoprotein via a stabilization mechanism.Biochemistry · 2015Article
- Amyloid-Forming Properties of Human Apolipoproteins: Sequence Analyses and Structural Insights.Advances in experimental medicine and biology · 2015Review
- Definition of human apolipoprotein A-I epitopes recognized by autoantibodies present in patients with cardiovascular diseases.The Journal of biological chemistry · 2014Article
- Molecular mechanisms of cellular cholesterol efflux.The Journal of biological chemistry · 2014Review
- The roles of C-terminal helices of human apolipoprotein A-I in formation of high-density lipoprotein particles.Biochimica et biophysica acta · 2014Article
- Significance of the hydrophobic residues 225-230 of apoA-I for the biogenesis of HDL.Journal of lipid research · 2013Article
- Mechanisms responsible for the compositional heterogeneity of nascent high density lipoprotein.The Journal of biological chemistry · 2013Article
- New insights into the determination of HDL structure by apolipoproteins: Thematic review series: high density lipoprotein structure, function, and metabolism.Journal of lipid research · 2013Review
- Factors controlling nascent high-density lipoprotein particle heterogeneity: ATP-binding cassette transporter A1 activity and cell lipid and apolipoprotein AI availability.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- Interactions of apolipoprotein A-I with high-density lipoprotein particles.Biochemistry · 2013Article
- Article
- Genetics of cholesterol efflux.Current atherosclerosis reports · 2012Review
- Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The apoA-I molecule adopts a two-domain tertiary structure and the properties of these domains modulate the ability to form HDL particles. Thus, human apoA-I differs from mouse apoA-I in that it can form smaller HDL particles; the C-terminal α-helix is important in this process and human apoA-I is unusual in containing aromatic amino acids in the non-polar face of this amphipathic α-helix. To understand the influence of these aromatic amino acids and the associated high hydrophobicity, apoA-I variants were engineered in which aliphatic amino acids were substituted with or without causing a decrease in overall hydrophobicity. The variants human apoA-I (F225L/F229A/Y236A) and apoA-I (F225L/F229L/A232L/Y236L) were compared to wild-type (WT) apoA-I for their abilities to (1) solubilize phospholipid vesicles and form HDL particles of different sizes, and (2) mediate cellular cholesterol efflux and create nascent HDL particles via ABCA1. The loss of aromatic residues and concomitant decrease in hydrophobicity in apoA-I (F225L/F229A/Y236A) has no effect on protein stability, but reduces by a factor of about three the catalytic efficiencies (V(max)/K(m)) of vesicle solubilization and cholesterol efflux; also, relatively large HDL particles are formed. With apoA-I (F225L/F229L/A232L/Y236L) where the hydrophobicity is restored by the presence of only leucine residues in the helix non-polar face, the catalytic efficiencies of vesicle solubilization and cholesterol efflux are similar to those of WT apoA-I; this variant forms smaller HDL particles. Overall, the results show that the hydrophobicity of the non-polar face of the C-terminal amphipathic α-helix plays a critical role in determining apoA-I functionality but aromatic amino acids are not required. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010).
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