Many amyloid precursors are intrinsically disordered initially, yet fold to highly organised cross-b structures during amyloid formation. How this conformational transition occurs structurally is not clear, with the initiating steps in aggregation being difficult to study because of the dynamics and heterogeneity of the species involved. It is also clear that the energy landscape for aggregation into amyloid could result in potentially many different amyloid folds. In this seminar I will discuss these concepts, drawing on recent results from our laboratory on the amyloidogenic proteins α-synuclein (αSyn) and islet associated polypeptide (IAPP). I will show how, by combining kinetic analysis of aggregation combined with structural analysis of intermediates and fibril structures, we are beginning to link the pathway of structural conversion from the initial unfolded monomer to the cross-b amyloid fold.

Sequence and structural features that control aggregation into amyloid

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.