Send to

Choose Destination
J Lipid Res. 2015 Aug;56(8):1531-42. doi: 10.1194/jlr.M059162. Epub 2015 May 28.

Thermal transitions in serum amyloid A in solution and on the lipid: implications for structure and stability of acute-phase HDL.

Author information

Department of Physiology & Biophysics, Boston University School of Medicine, Boston MA 02118.
Institute for Pharmaceutical Biotechnology, University of Ulm, 89081, Ulm, Germany.


Serum amyloid A (SAA) is an acute-phase protein that circulates mainly on plasma HDL. SAA interactions with its functional ligands and its pathogenic deposition in reactive amyloidosis depend, in part, on the structural disorder of this protein and its propensity to oligomerize. In vivo, SAA can displace a substantial fraction of the major HDL protein, apoA-I, and thereby influence the structural remodeling and functions of acute-phase HDL in ways that are incompletely understood. We use murine SAA1.1 to report the first structural stability study of human plasma HDL that has been enriched with SAA. Calorimetric and spectroscopic analyses of these and other SAA-lipid systems reveal two surprising findings. First, progressive displacement of the exchangeable fraction of apoA-I by SAA has little effect on the structural stability of HDL and its fusion and release of core lipids. Consequently, the major determinant for HDL stability is the nonexchangeable apoA-I. A structural model explaining this observation is proposed, which is consistent with functional studies in acute-phase HDL. Second, we report an α-helix folding/unfolding transition in SAA in the presence of lipid at near-physiological temperatures. This new transition may have potentially important implications for normal functions of SAA and its pathogenic misfolding.


circular dichroism spectroscopy; differential scanning calorimetry; exchangeable apolipoprotein A-I; high density lipoprotein; lipid-induced α-helix folding; protein-lipid interactions; thermodynamically irreversible transition

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center