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Fused in sarcoma undergoes cold denaturation: Implications on phase separation

Por um escritor misterioso

Descrição
The mediation of fused in sarcoma (FUS) protein liquid-liquid phase separation (LLPS) is generally attributed to the low-complexity and disordered domains, while the role of its folded domains remains unknown. In this work we questioned the role of the folded domains on the full-length (FL) FUS LLPS and studied the influence of several metabolites, ions and overall conditions on the LLPS process using turbidity assays, differential interference contrast microscopy and nuclear magnetic resonance spectroscopy. We demonstrate that FL FUS LLPS is highly responsive to the surrounding conditions, and that overall intrinsic disorder is crucial for LLPS. To promote such disorder, we reveal that the FUS RNA-recognition domain (RRM) and the zinc-finger motif (ZnF) undergo cold denaturation above 0ºC, at a temperature that is determined by the conformational stability of the ZnF domain. We hypothesize that, in cold shock conditions, cold denaturation might provide a pathway that exposes additional residues to promote FUS self-assembly. Such findings mark the first evidence that FUS globular domains may have an active role in stress granule formation in cold stress.
Fused in sarcoma undergoes cold denaturation: Implications on phase separation
Fused in sarcoma undergoes cold denaturation: Implications for phase separation - Félix - 2023 - Protein Science - Wiley Online Library
Fused in sarcoma undergoes cold denaturation: Implications on phase separation
Thermograms of IscU and of its mutants. a IscU_wt (no Zn²⁺, pale blue);
Fused in sarcoma undergoes cold denaturation: Implications on phase separation
Stability curves of IscU and mutants. Stability curves of IscU
Fused in sarcoma undergoes cold denaturation: Implications on phase separation
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Fused in sarcoma undergoes cold denaturation: Implications on phase separation
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Fused in sarcoma undergoes cold denaturation: Implications on phase separation
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Fused in sarcoma undergoes cold denaturation: Implications on phase separation
Fused in sarcoma undergoes cold denaturation: Implications on phase separation
Fused in sarcoma undergoes cold denaturation: Implications on phase separation
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Fused in sarcoma undergoes cold denaturation: Implications on phase separation
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Fused in sarcoma undergoes cold denaturation: Implications on phase separation
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Fused in sarcoma undergoes cold denaturation: Implications on phase separation
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Fused in sarcoma undergoes cold denaturation: Implications on phase separation
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Fused in sarcoma undergoes cold denaturation: Implications on phase separation
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Fused in sarcoma undergoes cold denaturation: Implications on phase separation
PDF] Fused in Sarcoma: Properties, Self-Assembly and Correlation with Neurodegenerative Diseases
Fused in sarcoma undergoes cold denaturation: Implications on phase separation
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