8QXB

TDP-43 amyloid fibrils: Morphology-2

Summary for 8QXB

• Entry DOI: 10.2210/pdb8qxb/pdb
• EMDB information: 18717
• Descriptor: TAR DNA-binding protein 43 (1 entity in total)
• Functional Keywords: amyloidosis, protein misfolding disease, amyloid fibrils, cryo electron microscopy, amyloid key, protein fibril
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 18
• Total formula weight: 806125.36

Authors

Sharma, K.,Shenoy, J.,Loquet, A.,Schmidt, M.,Faendrich, M. (deposition date: 2023-10-24, release date: 2024-01-24)

Primary citation

Sharma, K.,Stockert, F.,Shenoy, J.,Berbon, M.,Abdul-Shukkoor, M.B.,Habenstein, B.,Loquet, A.,Schmidt, M.,Fandrich, M.
Cryo-EM observation of the amyloid key structure of polymorphic TDP-43 amyloid fibrils.
Nat Commun, 15:486-486, 2024

PubMed 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.

PubMed: 38212334
DOI: 10.1038/s41467-023-44489-0

Experimental method

ELECTRON MICROSCOPY (3.86 Å)