Ziaunys, M.; Sulskis, D.; Mikalauskaite, K.; Sakalauskas, A.; Smirnovas, V.

Protein aggregation in the form of amyloid fibrils has long been associated with the onset and development of various amyloidoses, including Alzheimer's, Parkinson's or prion diseases. Recent studies of their fibril formation process have revealed that amyloidogenic protein cross-interactions may impact aggregation pathways and kinetic parameters, as well as the structure of the resulting aggregates. Despite a growing number of reports exploring this type of interaction, they only cover just a small number of possible amyloidogenic protein pairings. One such pair is between two neurodegeneration-associated proteins: S100A9 and prion protein, which are known to co-localize in vivo. In this study, we examine their cross-interaction in vitro and demonstrate that S100A9 has a significant influence on not only prion protein aggregation kinetics, but also selectively promotes the formation of a specific fibril conformation.