The low-complexity domain of the FUS RNA binding protein self-assembles via the mutually exclusive use of two distinct cross-β cores.
| Autor: | Kato M; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390; Steven.McKnight@UTSouthwestern.edu masato.kato@utsouthwestern.edu.; Institute for Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan., McKnight SL; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390; Steven.McKnight@UTSouthwestern.edu masato.kato@utsouthwestern.edu. |
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| Jazyk: | angličtina |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Oct 19; Vol. 118 (42). |
| DOI: | 10.1073/pnas.2114412118 |
| Abstrakt: | The low-complexity (LC) domain of the fused in sarcoma (FUS) RNA binding protein self-associates in a manner causing phase separation from an aqueous environment. Incubation of the FUS LC domain under physiologically normal conditions of salt and pH leads to rapid formation of liquid-like droplets that mature into a gel-like state. Both examples of phase separation have enabled reductionist biochemical assays allowing discovery of an N-terminal region of 57 residues that assembles into a labile, cross-β structure. Here we provide evidence of a nonoverlapping, C-terminal region of the FUS LC domain that also forms specific cross-β interactions. We propose that biologic function of the FUS LC domain may operate via the mutually exclusive use of these N- and C-terminal cross-β cores. Neurodegenerative disease-causing mutations in the FUS LC domain are shown to imbalance the two cross-β cores, offering an unanticipated concept of LC domain function and dysfunction. Competing Interests: The authors declare no competing interest. (Copyright © 2021 the Author(s). Published by PNAS.) |
| Databáze: | MEDLINE |
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