A possible role for π‐stacking in the self‐assembly of amyloid fibrils

Amyloid fibril formation is assumed to be the molecular basis for a variety of diseases of unrelated origin. Despite its fundamental clinical importance, the mechanism of amyloid formation is not fully understood. When we analyzed a variety of short functional fragments from unrelated amyloid-forming proteins, a remarkable occurrence of aromatic residues was observed. The finding of aromatic residues in diverse fragments raises the possibility that pi-pi interactions may play a significant role in the molecular recognition and self-assembly processes that lead to amyloid formation. This is in line with the well-known central role of pi-stacking interactions in self-assembly processes in the fields of chemistry…