ALPHA-HELICAL REQUIREMENTS FOR FREE APOLIPOPROTEINS TO GENERATE HDL AND TO INDUCE CELLULAR LIPID EFFLUX

The structural requirement has been studied for apolipoproteins in their free form to interact with cells, to generate high density lipoprotein (HDL), and to cause cellular lipid efflux (J. Biol Chem. 266, 3080-3086, 1991). It is shown that human apolipoprotein (apo) A-IV and apolipophorin III of Manduca sexta cause cholesterol efflux from cholesterol-loaded mouse peritoneal macrophages and reduce intracellularly accumulated cholesteryl ester as a result of forming HDL-like particles with cellular lipids, as do apoA-I, A-II and E. On the other hand, similar to apoC-III, reduced-and-carboxymethylated human apoA-II had no such effect. Thus, apolipoproteins seem to require at least four amphiphilic helical segments per molecule to express this function.