51. New insights on the structure of alpha-synuclein fibrils using cryo-electron microscopy
- Author
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Dongchun Ni, Henning Stahlberg, Lubomír Kováčik, and Ricardo C. Guerrero-Ferreira
- Subjects
0301 basic medicine ,Materials science ,Cryo-electron microscopy ,High resolution ,macromolecular substances ,Fibril ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Microscopy ,medicine ,Humans ,Cytoskeleton ,Alpha-synuclein ,Dementia with Lewy bodies ,General Neuroscience ,Cryoelectron Microscopy ,Parkinson Disease ,medicine.disease ,030104 developmental biology ,chemistry ,Transmission electron microscopy ,Mutation ,alpha-Synuclein ,Biophysics ,Neuroscience ,030217 neurology & neurosurgery ,Cellular inclusions - Abstract
Fibrils of alpha-synuclein are significant components of cellular inclusions associated with several neuropathological disorders including Parkinson’s disease, multiple system atrophy and dementia with Lewy bodies. In recent years, technological advances in the field of transmission electron microscopy and image processing have made it possible to solve the structure of alpha-synuclein fibrils at high resolution. This review discusses the results of structural studies using cryo-electron microscopy, which revealed that in-vitro produced fibrils vary in diameter from 5 nm for single-protofilament fibrils, to 10 nm for two-protofilament fibrils. In addition, the atomic models hint at contributions of the familial Parkinson’s disease mutation sites to inter-protofilament interaction and the locations where post-translational modifications take place. Here, we propose a nomenclature system that allows identifying the existing alpha-synuclein polymorphs and that will allow to incorporate additional high-resolution structures determined in the future.
- Published
- 2020