Identification of the Rigid Core for Aged Liquid Droplets of an RNA-Binding Protein Low Complexity Domain.

Autor:	Fonda BD; Department of Chemistry, University of California, Davis, California 95616, United States., Jami KM; Department of Chemistry, University of California, Davis, California 95616, United States., Boulos NR; Department of Chemistry, University of California, Davis, California 95616, United States., Murray DT; Department of Chemistry, University of California, Davis, California 95616, United States.
Jazyk:	angličtina
Zdroj:	Journal of the American Chemical Society [J Am Chem Soc] 2021 May 05; Vol. 143 (17), pp. 6657-6668. Date of Electronic Publication: 2021 Apr 25.
DOI:	10.1021/jacs.1c02424
Abstrakt:	The biomolecular condensation of proteins with low complexity sequences plays a functional role in RNA metabolism and a pathogenic role in neurodegenerative diseases. The formation of dynamic liquid droplets brings biomolecules together to achieve complex cellular functions. The rigidification of liquid droplets into β-strand-rich hydrogel structures composed of protein fibrils is thought to be purely pathological in nature. However, low complexity sequences often harbor multiple fibril-prone regions with delicately balanced functional and pathological interactions. Here, we investigate the maturation of liquid droplets formed by the low complexity domain of the TAR DNA-binding protein 43 (TDP-43). Solid state nuclear magnetic resonance measurements on the aged liquid droplets identify residues 365-400 as the structured core, which are squarely outside the region between residues 311-360 thought to be most important for pathological fibril formation and aggregation. The results of this study suggest that multiple segments of this low complexity domain are prone to form fibrils and that stabilization of β-strand-rich structure in one segment precludes the other region from adopting a rigid fibril structure.
Databáze:	MEDLINE
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