Apolipoprotein A-II Alters the Proteome of Human Lipoproteins and Enhances Cholesterol Efflux From ABCA1

J Lipid Res. 2017 Jul;58(7):1374-1385. doi: 10.1194/jlr.M075382. Epub 2017 May 5.

Abstract

HDLs are a family of heterogeneous particles that vary in size, composition, and function. The structure of most HDLs is maintained by two scaffold proteins, apoA-I and apoA-II, but up to 95 other "accessory" proteins have been found associated with the particles. Recent evidence suggests that these accessory proteins are distributed across various subspecies and drive specific biological functions. Unfortunately, our understanding of the molecular composition of such subspecies is limited. To begin to address this issue, we separated human plasma and HDL isolated by ultracentrifugation (UC-HDL) into particles with apoA-I and no apoA-II (LpA-I) and those with both apoA-I and apoA-II (LpA-I/A-II). MS studies revealed distinct differences between the subfractions. LpA-I exhibited significantly more protein diversity than LpA-I/A-II when isolated directly from plasma. However, this difference was lost in UC-HDL. Most LpA-I/A-II accessory proteins were associated with lipid transport pathways, whereas those in LpA-I were associated with inflammatory response, hemostasis, immune response, metal ion binding, and protease inhibition. We found that the presence of apoA-II enhanced ABCA1-mediated efflux compared with LpA-I particles. This effect was independent of the accessory protein signature suggesting that apoA-II induces a structural change in apoA-I in HDLs.

Keywords: ATP binding cassette transporter A1; high density lipoprotein/structure; proteomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1 / metabolism*
  • Apolipoprotein A-I / metabolism
  • Apolipoprotein A-II / metabolism*
  • Biological Transport
  • Humans
  • Proteome / metabolism*

Substances

  • ATP Binding Cassette Transporter 1
  • Apolipoprotein A-I
  • Apolipoprotein A-II
  • Proteome