Heparin interactions with apoA1 and SAA in inflammation-associated HDL

Research output: Contribution to journalArticle

Abstract

Apolipoprotein A1 (apoA1) is the main protein component responsible for transportation of cholesterol on high-density lipoprotein (HDL). Serum amyloid A (SAA) is an acute phase protein associated with HDL. Apart from their physiological functions, both apoA1 and SAA have been identified as 'amyloidogenic peptides'. We report herein that the polysaccharide heparin interacts with both apoA1 and SAA in HDL isolated from plasma of inflamed mice. The reaction is rapid, forming complex aggregates composed of heparin, apoA1 and SAA as revealed by gel electrophoresis. This interaction is dependent on the size and concentration of added heparin. Mass spectrometry analysis of peptides derived from chemically crosslinked HDL-SAA particles detected multiple crosslinks between apoA1 and SAA, indicating close proximity (within 25 Å) of these two proteins on the HDL surface, providing a molecular and structural mechanism for the simultaneous binding of heparin to apoA1 and SAA.

Details

Authors
  • Andreas Digre
  • Jie Nan
  • Martin Frank
  • Jin-Ping Li
Organisations
External organisations
  • Uppsala University
  • Biognos AB
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medicinal Chemistry
Original languageEnglish
Pages (from-to)309-14
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume474
Issue number2
Publication statusPublished - 2016 May 27
Publication categoryResearch
Peer-reviewedYes