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Structures of Pathological and Functional Amyloids and Prions, a Solid-State NMR Perspective

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.
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Submitted on : Friday, October 15, 2021 - 12:04:23 PM
Last modification on : Thursday, April 7, 2022 - 10:10:46 AM
Long-term archiving on: : Sunday, January 16, 2022 - 7:39:31 PM

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Asen Daskalov, Nadia El Mammeri, Alons Lends, Jayakrishna Shenoy, Gaelle Lamon, et al.. Structures of Pathological and Functional Amyloids and Prions, a Solid-State NMR Perspective. Frontiers in Molecular Neuroscience, Frontiers Media, 2021, 14, pp.670513. ⟨10.3389/fnmol.2021.670513⟩. ⟨pasteur-03379976⟩

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