The hallmark of ‘misfolding diseases’ such as Alzheimer’s, Huntington’s, Parkinson’s, and Multiple System Atrophy is conversion of initially soluble proteins into insoluble amyloid protein structures. The surrounding environment of the proteins, e.g. buffer conditions, location within organelles, and their interacting partners, e.g. proteins, ions, lipids, and water, can greatly influence their propensity to misfold. Discovering protein structures that are initially formed in the misfolding pathway and how the environment influences this will be key to understanding how these proteins function in health and disease. 

This methods collection will highlight techniques used to study monomeric amyloid proteins and their conversion into higher order structures, including oligomers, aggregates, and fibrils and how they interact with their surrounding environment, particularly investigating potential conformations and initial environmental triggers that can initiate misfolding. These include biophysical techniques (small angle neuron scattering (SANS)), spectroscopy, structural techniques (NMR, Mass Spectrometry – Hydrogen-Deuterium Exchange, Fast photochemical oxidation of proteins (FPOP), ion-mobility (IM-MS)) and imaging techniques (super-resolution microscopy, Atomic Force Microscopy (AFM)).