Interconversion between Serum Amyloid A Native and Fibril Conformations

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 k B T. Crucial for the assembly into the fibril structure is the salt bridge 26E–34K that provides a scaffold for forming the fibril conformation.