Fig. 8.

Hypothetical structural model of mature plasma HDL containing increasing amounts of SAA. The model that exemplifies nHDL shows four copies of apoA-I, including one molecular dimer in a double-belt conformation and two monomers in a putative double-hairpin conformation. For details of these conformations and alternative models, see (69) and references therein. The SAA:apoA-I molar ratios are indicated. Addition of SAA initially leads to its binding to the available HDL surface (0.5:1 SAA:apoA-I mol/mol), followed by progressive displacement of the exchangeable fraction of apoA-I. We propose that this readily exchangeable apoA-I is probably monomeric, while the less exchangeable apoA-I that determines HDL stability is dimeric. HDL incubation at 4:1 molar (or 1.7:1 weight) ratio of SAA:apoA-I, which displaces approximately two-thirds of apoA-I from HDL (Fig. 1), must be compensated by binding of at least an equivalent amount of SAA in order to maintain the particle density in the HDL₃ range. Thus, the HDL-bound proteins comprise roughly two-thirds SAA and one-third apoA-I by weight, which resembles their ratio in the incubation mixture. Such a ratio of bound SAA to apoA-I can be achieved if HDL contains 2 apoA-I molecules and 8 to 10 SAA molecules (right panel).