Conformational change of apolipoprotein A-I and HDL formation from model membranes under intracellular acidic conditions.
The molecular mechanism by which nascent HDL forms via the interaction of apolipoprotein A-I (apoA-I) and transmembrane ABCA1 is poorly understood. Here, because ABCA1 has been reported to localize to acidic intracellular compartments, including the Golgi and endosome, we studied the interaction of apoA-I with model membranes under acidic conditions. Pure phosphatidylcholine liposomes were persistent against apoA-I at pH levels above 5.0, but were progressively transformed into reconstituted HDLs (rHDLs) by apoA-I at lower pH. Circular dichroism spectral measurements and 8-anilino-1-naphthalenesulfonic acid fluorescence measurements of lipid-free apoA-I ascribed this accelerated rHDL formation to the conformational change of the protein into a rather hydrophobic alpha-helical structure under acidic conditions. The addition of phosphatidylserine (PS) increased acidity at the bilayer surface and enabled the formation of discoidal rHDLs even at the pH of the endosome and slightly lower pH of the Golgi. These results suggest the following new scenario of nascent HDL formation: ABCA1, which colocalizes with apoA-I in acidic intracellular compartments, including the Golgi and endosome, increases acidity at the membrane surface on the luminal side by PS translocase activity and causes apoA-I to form nascent HDL.
Fukuda
Masakazu
M
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Nakano
Minoru
M
Miyazaki
Masakazu
M
Tanaka
Masafumi
M
Saito
Hiroyuki
H
Kobayashi
Satoe
S
Ueno
Masaharu
M
Handa
Tetsurou
T
D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D008076:Cholesterol, HDL / Q000096:biosynthesis*; D002942:Circular Dichroism; D053442:High-Density Lipoproteins, Pre-beta / Q000096:biosynthesis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism*; D008081:Liposomes; D021962:Membrane Microdomains / Q000378:metabolism*; D008954:Models, Biological; D010713:Phosphatidylcholines / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D017433:Protein Structure, Secondary
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D053442:High-Density Lipoproteins, Pre-beta; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D010718:Phosphatidylserines