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TitleSeeded assembly in vitro does not replicate the structures of α-synuclein filaments from multiple system atrophy.
Journal, issue, pagesFEBS Open Bio, Vol. 11, Issue 4, Page 999-991013, Year 2021
Publish dateFeb 24, 2021
AuthorsSofia 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 AbstractThe 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 linksFEBS Open Bio / PubMed:33548114 / PubMed Central
MethodsEM (helical sym.)
Resolution3.18 - 4.23 Å
Structure data

12264

7nca

EMDB-12264, PDB-7nca:
Type 1A alpha-synuclein filament seeded in vitro by filaments purified from Multiple Systems Atrophy Case 2
Method: EM (helical sym.) / Resolution: 3.47 Å

12265

7ncg

EMDB-12265, PDB-7ncg:
Type 2A alpha-synuclein filament seeded in vitro by filaments purified from Multiple Systems Atrophy Case 2
Method: EM (helical sym.) / Resolution: 3.43 Å

12266

7nch

EMDB-12266, PDB-7nch:
Type 1B alpha-synuclein filament seeded in vitro by filaments purified from Multiple Systems Atrophy Case 1
Method: EM (helical sym.) / Resolution: 3.84 Å

12267

7nci

EMDB-12267, PDB-7nci:
Type 2B alpha-synuclein filament seeded in vitro by filaments purified from Multiple Systems Atrophy Case 1
Method: EM (helical sym.) / Resolution: 3.55 Å

12268

7ncj

EMDB-12268, PDB-7ncj:
Type 2AB alpha-synuclein filament seeded in vitro by filaments purified from Multiple Systems Atrophy Case 1
Method: EM (helical sym.) / Resolution: 4.23 Å

12269

7nck

EMDB-12269, PDB-7nck:
Type 3 alpha-synuclein filament seeded in vitro by filaments purified from Multiple Systems Atrophy Case 5
Method: EM (helical sym.) / Resolution: 3.18 Å

Source
  • homo sapiens (human)
KeywordsPROTEIN FIBRIL / Amyloid / Multiple System Atrophy / Neurodegeneration / alpha-synuclein / filament

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