Director and professor, Sheena E. Radford, Astbury Centre for Structural Molecular Biology, University of Leeds, United Kingdom

Molecular Dissection of Protein Misfolding Mechanisms

Understanding how different proteins assemble into the ordered, insoluble aggregates associated with amyloid disease is a formidable challenge. Whilst it is generally accepted that protein unfolding is required for the formation of amyloid fibrils from natively folded proteins in vitro and, therefore, presumably also in vivo, the point at which the folding and aggregation free energy landscapes diverge, and the role of different amino acid residues in determining folding versus aggregation, remain obscure. Even more challenging is the identification of early oligomeric species and their structural characterisation, since such species are aggregation-prone, short-lived and rapidly equilibrating.  In this lecture I will describe our recent experiments which have used an array of biophysical and biochemical methods to elucidate the mechanism by which the normally soluble protein, beta-2-microglobulin, converts into an amyloidogenic conformation and how bimolecular collisions between protein variants can result in very different outcomes of assembly. The insights gained may help to derive new routes to the modulation of aggregation and lead to fascinating questions about the cooperativity of protein structures and how this modulates their behaviours in amyloid assembly. 

Host: Professor Daniel Otzen, iNANO and Department of Molecular Biology and Genetics, Aarhus University, Aarhus

Coffee, tea and bread will be served in front of the iNANO auditorium from 10:00.