7NCA

Type 1A alpha-synuclein filament seeded in vitro by filaments purified from Multiple Systems Atrophy Case 2

Summary for 7NCA

• Entry DOI: 10.2210/pdb7nca/pdb
• EMDB information: 12264
• Descriptor: Alpha-synuclein (1 entity in total)
• Functional Keywords: amyloid, multiple system atrophy, neurodegeneration, alpha-synuclein, filament, protein fibril
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 12
• Total formula weight: 173713.30

Authors

Lovestam, S.K.A.,Schweighauser, M.,Scheres, S.H.W. (deposition date: 2021-01-28, release date: 2021-02-24, Last modification date: 2024-05-01)

Primary citation

Lovestam, S.,Schweighauser, M.,Matsubara, T.,Murayama, S.,Tomita, T.,Ando, T.,Hasegawa, K.,Yoshida, M.,Tarutani, A.,Hasegawa, M.,Goedert, M.,Scheres, S.H.W.
Seeded assembly in vitro does not replicate the structures of alpha-synuclein filaments from multiple system atrophy.
Febs Open Bio, 11:999-1013, 2021

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 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.

PubMed: 33548114
DOI: 10.1002/2211-5463.13110

Experimental method

ELECTRON MICROSCOPY (3.47 Å)