Abstract
Transactive response DNA-binding protein of 43 kDa (TDP-43) is a 414-residue protein whose aberrant aggregation is implicated in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) or frontotemporal lobar degeneration (FTLD). Intriguingly, TDP-43 has also been shown to functionally oligomerize to carry out physiological functions. TDP-43 also exists in mixed condensates or granules with other proteins (e.g. neuronal or stress granules), and its large C-terminal domain (CTD, residues 267–414) seems responsible for TDP-43 both homo- and heterotypic interactions underlying such diverse functional and pathological aggregation events. A myriad of distinct triggers may drive TDP-43 oligomerization, including interaction partners or changes in pH or salinity. In this Assignment Note, we report the complete backbone and a wealth of side chain chemical shift assignments for the CTD of TDP-43 at pH 4. The assignments presented here provide a solid starting point to study the aggregation pathway of TDP-43 at pH values below those considered physiological but relevant in pathological settings, and to contrast the aggregation behaviour under distinct conditions and in the presence of interacting partners.
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Acknowledgements
This work has been funded by Grants CTQ2017-84371-P to D.P.-U. and SAF2016-76678-C2-2-R to D.V.L., from the Spanish MINECO; Grant MCB1412253 from the U. S. National Science Foundation to A.E.M; AriSLA (PathensTDP project) to E.B.; and Grant LCF/BQ/PR19/11700003 from La Caixa Foundation (ID 100010434) to M.M. NMR experiments were performed in the “Manuel Rico” NMR Laboratory (LMR) of the Spanish National Research Council (CSIC), a node of the Spanish Large-Scale National Facility (ICTS R-LRB).
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Pantoja-Uceda, D., Stuani, C., Laurents, D.V. et al. NMR assignments for the C-terminal domain of human TDP-43. Biomol NMR Assign 15, 177–181 (2021). https://doi.org/10.1007/s12104-020-10002-7
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DOI: https://doi.org/10.1007/s12104-020-10002-7