HDL biology
CETP shrinks reconstituted HDL from 9.2 to 8.0 nm by swapping cholesteryl ester for triglyceride and losing an apoA-I molecule (J Biol Chem 1995)
Original title: The influence of cholesteryl ester transfer protein on the composition, size, and structure of spherical, reconstituted high density lipoproteins
Spherical reconstituted HDL containing apoA-I as sole apolipoprotein were incubated with CETP and a triglyceride-rich emulsion for up to 24 hours. CETP promoted transfer of cholesteryl ester out of and triglyceride into the reconstituted particles, and because cholesteryl ester loss exceeded triglyceride gain, core lipid content fell, shrinking particle diameter from 9.2 to 8.0 nm, with apoA-I dissociating and particle apoA-I content falling from three to two molecules per particle. Spectroscopy showed the resulting 8.0-nm particles had a more polar, hydrated lipid-water interface and less ordered phospholipid packing, with three exposed apoA-I tryptophan residues versus two in the 9.2-nm particles, though alpha-helical content and surface charge were unchanged and apoA-I was actually more stable to guanidine denaturation in the smaller particle, showing CETP remodels HDL into small, triglyceride-enriched, apoA-I-depleted particles with an altered but more stable surface.
Original abstract
The effect of cholesteryl ester transfer protein (CETP) on the size, composition, and structure of spherical, reconstituted HDL (rHDL) which contain apolipoprotein (apo) A-I as their sole apolipoprotein has been studied. Spherical rHDL were incubated with CETP and Intralipid for up to 24 h. During this time CETP promoted transfers of cholesteryl esters (CE) and triglyceride (TG) between rHDL and Intralipid. As a result, the rHDL became depleted of CE and enriched in TG. However, as the loss of CE from the rHDL was greater than the gain of TG, the concentration of core lipids in the rHDL decreased. The decrease in the concentration of rHDL core lipids, which was evident throughout the incubation, was accompanied by a reduction in rHDL diameter from 9.2 to 8.0 nm, the dissociation of apoA-I from rHDL and a decrease in the number of apoA-I molecules, from three/particle in the 9.2-nm rHDL, to two/particle in the 8.0-nm rHDL. Spectroscopic studies showed that the lipid-water interface and phospholipid packing of the 8.0-nm rHDL were, respectively, more polar and less ordered than those of the 9.2-nm rHDL. Quenching studies with KI revealed that the number of exposed apoA-I Trp residues in the 9.2- and 8.0-nm rHDL was two and three, respectively. Circular dichroism established that the 9.2- and 8.0-nm rHDL had identical apoA-I alpha-helical contents. The 9.2- and 8.0-nm rHDL also had identical surface charges as determined by agarose gel electrophoresis. Denaturation studies with guanidine hydrochloride demonstrated that apoA-I is more stable in 8.0-nm rHDL than in 9.2-nm rHDL. It is concluded that CETP converts rHDL to small, TG-enriched, apoA-I-depleted particles with increased lipid-water interfacial hydration and less ordered phospholipid packing. These changes are associated with enhanced stability and minor changes to the conformation of the apoA-I which remains associated with the rHDL.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.