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 SAA(1-76). Using Replica Exchange with Tunneling, we study the conversion of a SAA(1-76) 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.

Automated summary

Overexpression of SAA can lead to amyloidosis. Using Replica Exchange with Tunneling, the conversion of SAA(1-76) chain was studied, finding the crucial role of salt bridge 26E-34K in fibril formation.