Cryo-EM observation of the amyloid key structure of polymorphic TDP-43 amyloid fibrils
Loading...
Date
2024-01-12
Authors
Sharma, Kartikay
Stockert, Fabian
Shenoy, Jayakrishna
Berbon, Mélanie
Abdul-Shukkoor, Muhammed Bilal
Habenstein, Birgit
Loquet, Antoine
Schmidt, Matthias
Fändrich, Marcus
Journal Title
Journal ISSN
Volume Title
Publication Type
Wissenschaftlicher Artikel
Published in
Nature Communications, 2024
Abstract
The transactive response DNA-binding protein-43 (TDP-43) is a multi-facet protein involved in phase separation, RNA-binding, and alternative splicing. In the context of neurodegenerative diseases, abnormal aggregation of TDP-43 has been linked to amyotrophic lateral sclerosis and frontotemporal lobar degeneration through the aggregation of its C-terminal domain. Here, we report a cryo-electron microscopy (cryo-EM)-based structural characterization of TDP-43 fibrils obtained from the full-length protein. We find that the fibrils are polymorphic and contain three different amyloid structures. The structures differ in the number and relative orientation of the protofilaments, although they share a similar fold containing an amyloid key motif. The observed fibril structures differ from previously described conformations of TDP-43 fibrils and help to better understand the structural landscape of the amyloid fibril structures derived from this protein.
Description
Faculties
Fakultät für Naturwissenschaften
Institutions
Institut für Proteinbiochemie
Citation
DFG Project uulm
EU Project THU
iNEXT-Discovery / Infrastructure for transnational access and discovery in structural biology / EC / H2020 / 871037
Other projects THU
License
CC BY 4.0 International
Is version of
Has version
Supplement to
Supplemented by
Has erratum
Erratum to
Has Part
Part of
DOI external
DOI external
10.1038/s41467-023-44489-0
Institutions
Periodical
Degree Program
DFG Project THU
item.page.thu.projectEU
item.page.thu.projectOther
Series
Keywords
Cryoelectron microscopy, Protein aggregation, DDC 540 / Chemistry & allied sciences