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J Lipid Res. 2013 Jun;54(6):1589-97. doi: 10.1194/jlr.M034785. Epub 2013 Apr 10.

Comparison of apoA-I helical structure and stability in discoidal and spherical HDL particles by HX and mass spectrometry.

Author information

1
Lipid Research Group, Gastroenterology, Hepatology, and Nutrition Division, Children's Hospital of Philadelphia, Philadelphia, PA 19104-4318, USA.

Abstract

Elucidation of apoA-I secondary structure in spherical plasma HDL particles is essential for understanding HDL structure and function at the molecular level. To provide this information, we have applied hydrogen exchange (HX) and mass spectrometry methods to compare apoA-I secondary structure in discoidal (two apoA-I molecules/particle) and spherical (five apoA-I molecules/particle) HDL particles. The HX kinetics indicate that the locations of helical segments within the apoA-I molecules are the same in both discoidal and spherical HDL particles (approximately 10 nm hydrodynamic diameter). Helix stabilities in both types of particles are 3-5 kcal/mol, consistent with the apoA-I molecules being in a highly dynamic state with helical segments unfolding and refolding in seconds. For the spherical HDL, apoA-I fragments corresponding to residues 115-158 exhibit bimodal HX kinetics consistent with this segment adopting an inter-converting (on the timescale of tens of minutes) helix-loop configuration. The segment adopting this configuration in the 10 nm disc is shorter because the surface area available to each apoA-I molecule is apparently larger. Loop formation in the central region of the apoA-I molecule contributes to the ability of the protein to adapt to changes in available space on the HDL particle surface. Overall, apoA-I secondary structure is largely unaffected by a change in HDL particle shape from disc to sphere.

KEYWORDS:

amphipathic α-helix; cholesterol; hydrogen exchange; lipoprotein; phospholipid

PMID:
23580759
PMCID:
PMC3646460
DOI:
10.1194/jlr.M034785
[Indexed for MEDLINE]
Free PMC Article
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