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-Structure paper
Title | Seeded assembly in vitro does not replicate the structures of α-synuclein filaments from multiple system atrophy. |
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Journal, issue, pages | FEBS Open Bio, Vol. 11, Issue 4, Page 999-991013, Year 2021 |
Publish date | Feb 24, 2021 |
Authors | Sofia Lövestam / Manuel Schweighauser / Tomoyasu Matsubara / Shigeo Murayama / Taisuke Tomita / Takashi Ando / Kazuko Hasegawa / Mari Yoshida / Airi Tarutani / Masato Hasegawa / Michel Goedert / Sjors H W Scheres / |
PubMed Abstract | The propagation of conformational strains by templated seeding is central to the prion concept. Seeded assembly of α-synuclein into filaments is believed to underlie the prion-like spreading of ...The propagation of conformational strains by templated seeding is central to the prion concept. Seeded assembly of α-synuclein into filaments is believed to underlie the prion-like spreading of protein inclusions in a number of human neurodegenerative diseases, including Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). We previously determined the atomic structures of α-synuclein filaments from the putamen of five individuals with MSA. Here, we used filament preparations from three of these brains for the in vitro seeded assembly of recombinant human α-synuclein. We find that the structures of the seeded assemblies differ from those of the seeds, suggesting that additional, as yet unknown, factors play a role in the propagation of the seeds. Identification of these factors will be essential for understanding the prion-like spreading of α-synuclein proteinopathies. |
External links | FEBS Open Bio / PubMed:33548114 / PubMed Central |
Methods | EM (helical sym.) |
Resolution | 3.18 - 4.23 Å |
Structure data | EMDB-12264, PDB-7nca: EMDB-12265, PDB-7ncg: EMDB-12266, PDB-7nch: EMDB-12267, PDB-7nci: EMDB-12268, PDB-7ncj: EMDB-12269, PDB-7nck: |
Source |
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Keywords | PROTEIN FIBRIL / Amyloid / Multiple System Atrophy / Neurodegeneration / alpha-synuclein / filament |