Interconversion between Serum Amyloid A Native and Fibril Conformations.

Abstract

Overexpression of serum amyloid A (SAA) can lead to a form of amyloidosis where the fibrils are made of SAA fragments, most often SAA1–76. Using Replica Exchange with Tunneling, we study the conversion of a SAA1–76 chain between the folded conformation and a fibril conformation. We find that the basins in the free energy landscape corresponding to the two motifs are separated by barriers of only about 2–3 kBT. Crucial for the assembly into the fibril structure is the salt bridge 26E–34K that provides a scaffold for forming the fibril conformation.