Electrostatic Interactions at N- and C-Termini Determine Fibril Polymorphism in Serum Amyloid A Fragments.

Amyloid polymorphism presents a challenge to physical theories of amyloid formation and stability. The amyloidogenic protein serum amyloid A (SAA) exhibits complex and unexplained structural polymorphism in its N-terminal fragments: the N-terminal 11-residue peptide (SAA1-11) forms left-handed helical fibrils, while extension by one residue (SAA1-12) produces a rare right-handed amyloid. In this study, we use a combination of vibrational spectroscopy and ultramicroscopy to examine fibrils of these peptides and their terminally acetylated and amidated variants, in an effort to uncover the physical basis for this effect.