Nicholas Frame, Shobini Jayaraman and Olga Gursky
Department of Physiology & Biophysics, Boston University School of Medicine, 700 Albany St. Boston MA 02118, USA
Serum amyloid A (SAA) is an acute-phase protein whose function is subject to debate. In acute injury, plasma levels of SAA can increase 1000-fold. Although functional ramifications of this dramatic increase are unclear, SAA may help remove lipids from damaged cells. SAA circulates mainly on plasma high-density lipoproteins (HDL), which are ~10 nm particles that remove excess cell cholesterol and protect against atherosclerosis. SAA can bind to HDL and replace its major protein, apoA-I. Alternatively, SAA can generate HDL de novo at the plasma membrane. To better understand this process, we analyzed interactions of SAA1.1with physiological phospholipid, POPC. SAA-POPC binding was monitored using circular dichroism spectroscopy, electron microscopy and gel electrophoresis. The results revealed that, in contrast to apoA-I, SAA can spontaneously remodel POPC vesicles to form ~10 nm HDL-like particles. Distinct stages of this remodeling were characterized by varying protein:lipid ratio. The major shift from lipid-free protein to HDL-like lipoprotein was observed between 1:2 and 1:5 SAA:POPC. This novel incremental transition mimics aspects of de novo generation of SAA-containing HDL. Similar particles may contribute to lipid removal from injured cells. Moreover, helix folding on the lipid observed in our work may protect SAA from cleavage and amyloid deposition in inflammation-linked amyloidosis.