AUTHOR=Daskalov Asen , El Mammeri Nadia , Lends Alons , Shenoy Jayakrishna , Lamon Gaelle , Fichou Yann , Saad Ahmad , Martinez Denis , Morvan Estelle , Berbon Melanie , Grélard Axelle , Kauffmann Brice , Ferber Mathias , Bardiaux Benjamin , Habenstein Birgit , Saupe Sven J. , Loquet Antoine TITLE=Structures of Pathological and Functional Amyloids and Prions, a Solid-State NMR Perspective JOURNAL=Frontiers in Molecular Neuroscience VOLUME=14 YEAR=2021 URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2021.670513 DOI=10.3389/fnmol.2021.670513 ISSN=1662-5099 ABSTRACT=

Infectious proteins or prions are a remarkable class of pathogens, where pathogenicity and infectious state correspond to conformational transition of a protein fold. The conformational change translates into the formation by the protein of insoluble amyloid aggregates, associated in humans with various neurodegenerative disorders and systemic protein-deposition diseases. The prion principle, however, is not limited to pathogenicity. While pathological amyloids (and prions) emerge from protein misfolding, a class of functional amyloids has been defined, consisting of amyloid-forming domains under natural selection and with diverse biological roles. Although of great importance, prion amyloid structures remain challenging for conventional structural biology techniques. Solid-state nuclear magnetic resonance (SSNMR) has been preferentially used to investigate these insoluble, morphologically heterogeneous aggregates with poor crystallinity. SSNMR methods have yielded a wealth of knowledge regarding the fundamentals of prion biology and have helped to solve the structures of several prion and prion-like fibrils. Here, we will review pathological and functional amyloid structures and will discuss some of the obtained structural models. We will finish the review with a perspective on integrative approaches combining solid-state NMR, electron paramagnetic resonance and cryo-electron microscopy, which can complement and extend our toolkit to structurally explore various facets of prion biology.