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bioRxiv · 10.1101/2021.12.05.471332

Functional Anatomy of the TDP-43 Redox Sensor

zhou, x.·Sumrow, L.·Sutherland, L.·Liu, D.·Qin, T.·McKnight, S. L.·Liszczak, G.
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Abstract

TAR binding protein 43 (TDP-43) is an RNA binding protein that assists in the maturation, export and sub-cellular localization of mRNA. The carboxyl terminal 153 residues of TDP-43 are of low sequence complexity and allow for self-association of the protein in a manner leading to its phase separation from an aqueous environment. These interactions assist TDP-43 in forming cytoplasmic RNA granules involved in the transport of mRNA for localized translation. Self-association of the TDP-43 low complexity (LC) domain is facilitated by a region of twenty five residues that are of extreme evolutionary conservation. The molecular basis for self-adherence of the protein through this region has been illuminated by a combination of structural and biochemical studies, allowing definition of a morphologically specific cross-{beta} structure predicted to be weakly assembled by main chain hydrogen bonds. In this study we have investigated the importance of individual, Pauling hydrogen bonds hypothesized to facilitate self-adherence of the TDP-43 LC domain.

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zhou, x., Sumrow, L., Sutherland, L., Liu, D., Qin, T., McKnight, S. L., Liszczak, G.. 2021-12-06. Functional Anatomy of the TDP-43 Redox Sensor. https://doi.org/10.1101/2021.12.05.471332

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