bioRxivBiophysics
The N-terminal domain of ALS-linked TDP-43 assembles without misfolding
P. S. Tsoi, K. J. Choi, P. G. Leonard, A. Sizovs, M. M. Moosa, K. R. MacKenzie, J. C. Ferreon, A. C. M. Ferreon
Abstract
TDP-43 forms inclusions in several neurodegenerative diseases, and both its N- and C-terminal domains are implicated in this process. We show that the folded TDP-43 N-terminal domain oligomerizes under physiological conditions and propose that, in full-length TDP-43, association between folded N-terminal domains enhances the propensity of the intrinsically unfolded C-terminal domains to drive pathological aggregation.
- organism: human
- assay: protein structure
- research focus: protein folding & dynamics
- approach: experimental assay
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