Hypothetical structure of human serum amyloid A protein

Abstract

The proteins known as serum amyloid A (SAA) play major, but relatively uncharacterized, roles in the acute phase response and are important components of the innate immune system of humans and probably all vertebrates. N-terminal fragments of the inducible isoforms, SAA1 and SAA2, are the major constituents of fibrils formed during secondary or reactive amyloidosis. Little is known about the structure of SAA beyond secondary structure analyses and circular dichroism spectroscopic data indicating significant alpha helix conformation. Analysis of the primary structure of human SAA indicates probable homology to the N-terminal domain of hemocyanins of arthropods and suggests that approximately 80% of the molecule may consist of a helical bundle with the remaining portion of the C-terminus potentially disordered. This model of SAA suggests that proposed binding sites for laminin, fibronectin, and calcium are segregated to one face of the molecule and that the heparin/heparan binding site is found in the putatively disordered region of the protein. It is possible that removal of the N-terminal 76 amino acid fragment by proteolytic cleavage found generates an unstable entity that undergoes a helix to beta strand transition analogous to the fibril process of A-beta and prion peptides.