Abstract

Macromolecular self-association plays a fundamental role in numerous biological processes ranging from host-pathogen interaction, viral infection to the propagation of neurodegenerative disorders. The assembled objects contain multiple protein subunits non-covalently arranged in supramolecular architectures that can execute a variety of cellular functions or cause detrimental consequences. Despite the large arsenal of biophysical approaches it remains a major challenge to provide atomic details on the assembled structures and the mechanisms involved in their assembly and function. Magic angle spinning solid-state NMR emerges as a powerful and versatile technique to reveal structures, dynamics and inter-molecular interactions in large macromolecular assemblies at the atomic scale without being limited by the size or the microscopic homogeneity of the objects. I will present MAS solid-state NMR methods and their application to two different types of molecular objects of pharmaceutical interest. I will concentrate on the insights we can obtain on functional amyloids involved in cell-death signaling but I will also introduce SSNMR approaches to discern structures of molecular machines involved in bacterial infection, the type 1 pilus and the type III secretion system needle.