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TitleTau filaments with the Alzheimer fold in cases with mutations V337M and R406W.
Journal, issue, pagesbioRxiv, Year 2024
Publish dateApr 30, 2024
AuthorsChao Qi / Sofia Lövestam / Alexey G Murzin / Sew Peak-Chew / Catarina Franco / Marika Bogdani / Caitlin Latimer / Jill R Murrell / Patrick W Cullinane / Zane Jaunmuktane / Thomas D Bird / Bernardino Ghetti / Sjors H W Scheres / Michel Goedert /
PubMed AbstractFrontotemporal dementia (FTD) and Alzheimer's disease are the most common forms of early-onset dementia. Dominantly inherited mutations in , the microtubule-associated protein tau gene, cause FTD and ...Frontotemporal dementia (FTD) and Alzheimer's disease are the most common forms of early-onset dementia. Dominantly inherited mutations in , the microtubule-associated protein tau gene, cause FTD and parkinsonism linked to chromosome 17 (FTDP-17). Individuals with FTDP-17 develop abundant filamentous tau inclusions in brain cells. Here we used electron cryo-microscopy to determine the structures of tau filaments from the brains of individuals with mutations V337M and R406W. Both mutations gave rise to tau filaments with the Alzheimer fold, which consisted of paired helical filaments in all V337M and R406W cases and of straight filaments in two V337M cases. We also identified a new assembly of the Alzheimer fold into triple tau filaments in a V337M case. Filaments assembled from recombinant tau(297-391) with mutation V337M had the Alzheimer fold and showed an increased rate of assembly.
External linksbioRxiv / PubMed:38746388 / PubMed Central
MethodsEM (helical sym.)
Resolution2.8 - 3.0 Å
Structure data

19854

9eog

EMDB-19854, PDB-9eog:
PHF type tau filament from R406W mutant
Method: EM (helical sym.) / Resolution: 3.0 Å

19855

9eoh

EMDB-19855, PDB-9eoh:
PHF type tau filament from in vitro V337M mutant
Method: EM (helical sym.) / Resolution: 2.8 Å

Source
  • homo sapiens (human)
KeywordsPROTEIN FIBRIL / TF / tau filament / R406W / PHF / V337M

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