Considerable progress has been made, using experiments and computations, to decipher the general principles governing the mechanism of formation of oligomers and fibrils of amyloid proteins implicated in diseases. The formation of amyloid aggregates is often observed to proceed from intrinsically disordered protein monomers to a highly ordered fibrillar state. Moreover, changes in sequence and environment may lead to a variety of polymorphs of the fibril state. I will discuss recent work exploring the connection between the conformational distribution of the monomeric protein and the ultimate fibril state. Examples will be taken from studies of amyloid-β protein (Aβ), associated with Alzheimer’s disease (AD), Fused in Sarcoma FUS) protein, implicated in ALS and liquid-liquid phase separation, and Serum Amyloid A (SAA)protein, associated with AA amyloidosis.

Hôte : Martin Weik (IBS/Dynamique et Cinétique des Processus Moléculaire)