Fused in sarcoma undergoes cold denaturation: Implications on phase separation
Por um escritor misterioso
Last updated 31 maio 2024
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.
The cold denaturation of IscU highlights structure-function dualism in marginally stable proteins. - Abstract - Europe PMC
Fused in sarcoma undergoes cold denaturation: Implications on phase separation
Cold Denaturation of the HIV-1 Protease Monomer
Liquid–Liquid Phase Separation and Its Mechanistic Role in Pathological Protein Aggregation - ScienceDirect
Fused in sarcoma undergoes cold denaturation: Implications on phase separation
Ectopic biomolecular phase transitions: fusion proteins in cancer pathologies: Trends in Cell Biology
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Temperature-Controlled Liquid–Liquid Phase Separation of Disordered Proteins
Cold shock causes energy depletion and AMPK activation. (A) COS7 cells
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Fused in sarcoma undergoes cold denaturation: Implications on phase separation
Temperature-Controlled Liquid–Liquid Phase Separation of Disordered Proteins
Temperature-Controlled Liquid–Liquid Phase Separation of Disordered Proteins
Temperature-Controlled Liquid–Liquid Phase Separation of Disordered Proteins
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