Structure and function of the apoA-IV T347S and Q360H common variants

Biochemical and Biophysical Research Communications
Monica GomaraschiLaura Calabresi

Abstract

Human apolipoprotein A-IV (apoA-IV) is involved in chylomicron assembly and secretion, and in reverse cholesterol transport. Several apoA-IV isoforms exist, the most common in Caucasian populations being apoA-IV-1a (T347S) and apoA-IV-2 (Q360H). The objective of the present study was to investigate the impact of these common aminoacid substitutions on the ability of apoA-IV to bind lipids, to promote cell cholesterol efflux via ABCA1, and to maintain endothelial homeostasis. Recombinant forms of wild-type apoA-IV, apoA-IV Q360H, and apoA-IV T347S were produced in Escherichia coli. ApoA-IV Q360H and apoA-IV T347S showed a slightly higher alpha-helical content compared to wild-type apoA-IV, and associated with phospholipids faster than wild-type apoA-IV. The capacity to promote ABCA1-mediated cholesterol efflux was significantly greater for the apoA-IV T347S than the other apoA-IV isoforms. No differences were observed in the ability of apoA-IV isoforms to inhibit the production of VCAM-1 and IL-6 in TNFalpha-stimulated endothelial cells. In conclusion, the apoA-IV T347S common variant has increased lipid binding properties and cholesterol efflux capacity, while the apoA-IV Q360H variant has only slightly increased lipid binding ...Continue Reading

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Citations

Apr 8, 2011·Age·Mónica Santos-GonzálezJosé M Villalba
Apr 17, 2012·Journal of Lipid Research·Katya B RubinowStephanie T Page
Dec 12, 2012·Biochemical Pharmacology·Monica GomaraschiLaura Calabresi
Oct 18, 2011·Biochimica Et Biophysica Acta·Changting Xiao, Gary F Lewis
Jul 15, 2016·Human Molecular Genetics·Claudia LaminaFlorian Kronenberg
Feb 3, 2015·Journal of Lipid Research·Fei WangPatrick Tso
Sep 6, 2020·Journal of Neurochemistry·Steve PedriniRalph N Martins

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