The essential building block of all HDL particles (or at least the vast majority of HDL particles) is a very special protein, first characterized and sequenced by Bryan Brewer at the US National Institutes of Health (NIH) in the late 1970s[4],[5],[6] and labeled apolipoprotein A-I, or apoA-I. Together with Jere Segrest at the University of Alabama at Birmingham (UAB), these investigators showed that apoA-I consists of a series of special helical structures, called amphipathic helices (Figure). These amphipathic helices have one side that is charged and has affinity for the aqueous phase, and the opposite side has an alignment of amino acid residues that are primarily hydrophobic and bind to lipid. These different amphipathic helices within ApoA-I are joined by what is called hinge regions, which are absolutely critical in rendering ApoA-I a very plastic protein. In other words, the fact that ApoA-I is so flexible means that it can assume several different types of structures, and this has major implications for HDL biology.
J Clin Lipidol. 2011; 5(6).[4]Gwynne J, Brewer HB, Edelhoch H. The molecular behavior of apoa-i in human high density lipoproteins. J Biol Chem 1976; 260():2269-2274.
[5]Brewer HB, Fairwell T, LaRue A, et al. The amino acid sequence of human Apoa-I, an apolipoprotein isolated from high density lipoproteins. Biochem Biophys Res Comm 1978;80(3):623-630.
[6]Segrest JP, Jackson RL, Morisette JD, Gotto AM Jr. A molecular theory of lipid-protein interactions in the plasma lipoproteins, FEBS Lett. 1974; 38: 247–258.
