title: Characterization of the oligomerization and aggregation of human Serum Amyloid A.
abstract: The fibrillation of Serum Amyloid A (SAA) - a major acute phase protein - is believed to play a role in the disease Amyloid A (AA) Amyloidosis. To better understand the amyloid formation pathway of SAA, we characterized the oligomerization, misfolding, and aggregation of a disease-associated isoform of human SAA - human SAA1.1 (hSAA1.1) - using techniques ranging from circular dichroism spectroscopy to atomic force microscopy, fluorescence spectroscopy, immunoblot studies, solubility measurements, and seeding experiments. We found that hSAA1.1 formed alpha helix-rich, marginally stable oligomers in vitro on refolding and cross-beta-rich aggregates following incubation at 37°C. Strikingly, while hSAA1.1 was not highly amyloidogenic in vitro, the addition of a single N-terminal methionine residue significantly enhanced the fibrillation propensity of hSAA1.1 and modulated its fibrillation pathway. A deeper understanding of the oligomerization and fibrillation pathway of hSAA1.1 may help elucidate its pathological role.
authors.affiliation: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York, USA.
authors.forename: Sanket
authors.initials: S
authors.lastname: Patke
authors.forename: Saipraveen
authors.initials: S
authors.lastname: Srinivasan
authors.forename: Ronak
authors.initials: R
authors.lastname: Maheshwari
authors.forename: Sunit K
authors.initials: SK
authors.lastname: Srivastava
authors.forename: J Javier
authors.initials: JJ
authors.lastname: Aguilera
authors.forename: Wilfredo
authors.initials: W
authors.lastname: Colón
authors.forename: Ravi S
authors.initials: RS
authors.lastname: Kane
mesh_terms: D006801:Humans; D008715:Methionine; D008958:Models, Molecular; D020033:Protein Isoforms / Q000737:chemistry; D055503:Protein Multimerization; D058849:Protein Refolding; D017433:Protein Structure, Secondary; D000685:Serum Amyloid A Protein / Q000737:chemistry*; D012995:Solubility
chemical_list: D020033:Protein Isoforms; D000685:Serum Amyloid A Protein; D008715:Methionine