Heparin interactions with apoA1 and SAA in inflammation-associated HDL.
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.
Department of Medical Biochemistry and Microbiology/SciLifeLab, University of Uppsala, The Biomedical Center, Box 582, SE-751 23 Uppsala, Sweden.
Andreas
A
Digre
MAX IV Laboratory, Lund University, P.O. Box 118, SE-221 00 Lund, Sweden.
Jie
J
Nan
Biognos AB, Box 8963, Gothenburg, Sweden.
Martin
M
Frank
Department of Medical Biochemistry and Microbiology/SciLifeLab, University of Uppsala, The Biomedical Center, Box 582, SE-751 23 Uppsala, Sweden. Electronic address: jin-ping.li@imbim.uu.se.
Jin-Ping
JP
Li
D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood*; D006493:Heparin / Q000097:blood*; D007249:Inflammation / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D000685:Serum Amyloid A Protein / Q000378:metabolism*
D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D000685:Serum Amyloid A Protein; D006493:Heparin
Amyloid; Atherosclerosis; Heparan sulfate; Lipoproteins/receptors; Mass spectrometry; Proteoglycans