Interconversion between Serum Amyloid A native and fibril conformations

Abstract

AbstractOverexpression 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 a 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.