Fused in sarcoma undergoes cold denaturation

Detalhes bibliográficos
Autor(a) principal: Félix, Sara S.
Data de Publicação: 2023
Outros Autores: Laurents, Douglas V., Oroz, Javier, Cabrita, Eurico J.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/150809
Resumo: Funding Information: The authors would also like to acknowledge Prof. Dr. Jaime Mota, Dra. Irina Franco for the technical assistance with the microscopic experiments, Philip O'Toole for the aid in protein production and Dr. Aldino Viegas and Dr. David Pantoja-Uceda for the support and valuable discussions regarding NMR spectroscopy. The authors also thank FCT-Portugal for the PhD grant attributed to SF (PD/BD/148028/2019) under the PTNMRPhD Program. JO is a recipient of a Leonardo Grant from the Spanish BBVA Foundation (BBM_TRA_0203) and a Ramón y Cajal Grant (RYC2018-026042-I funded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future.”) JO and DVL are supported by the Spanish Grants PID-2019-109276RA-I00 and PID-2019-109306RB-I00, respectively, both funded by MCIN/AEI/10.13039/501100011033. The NMR spectrometers are part of the National NMR Facility supported by FCT-Portugal (ROTEIRO/0031/2013–PINFRA/22161/2016, co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). The 800 MHz spectrometer present in the “Manuel Rico” NMR laboratory (LMR-CSIC) is a node of the Spanish Large-Scale National Facility (ICTS R-LRB-MR). Publisher Copyright: © 2022 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.
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spelling Fused in sarcoma undergoes cold denaturationImplications for phase separationcold denaturationcold stressfused in sarcoma (FUS)liquid–liquid phase separation (LLPS)nuclear magnetic resonance (NMR)BiochemistryMolecular BiologyFunding Information: The authors would also like to acknowledge Prof. Dr. Jaime Mota, Dra. Irina Franco for the technical assistance with the microscopic experiments, Philip O'Toole for the aid in protein production and Dr. Aldino Viegas and Dr. David Pantoja-Uceda for the support and valuable discussions regarding NMR spectroscopy. The authors also thank FCT-Portugal for the PhD grant attributed to SF (PD/BD/148028/2019) under the PTNMRPhD Program. JO is a recipient of a Leonardo Grant from the Spanish BBVA Foundation (BBM_TRA_0203) and a Ramón y Cajal Grant (RYC2018-026042-I funded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future.”) JO and DVL are supported by the Spanish Grants PID-2019-109276RA-I00 and PID-2019-109306RB-I00, respectively, both funded by MCIN/AEI/10.13039/501100011033. The NMR spectrometers are part of the National NMR Facility supported by FCT-Portugal (ROTEIRO/0031/2013–PINFRA/22161/2016, co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). The 800 MHz spectrometer present in the “Manuel Rico” NMR laboratory (LMR-CSIC) is a node of the Spanish Large-Scale National Facility (ICTS R-LRB-MR). Publisher Copyright: © 2022 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.The mediation of liquid–liquid phase separation (LLPS) for fused in sarcoma (FUS) protein is generally attributed to the low-complexity, disordered domains and is enhanced at low temperature. The role of FUS folded domains on the LLPS process remains relatively unknown since most studies are mainly based on fragmented FUS domains. Here, we investigate the effect of metabolites on full-length (FL) FUS LLPS using turbidity assays and differential interference contrast (DIC) microscopy, and explore the behavior of the folded domains by nuclear magnetic resonance (NMR) spectroscopy. FL FUS LLPS is maximal at low concentrations of glucose and glutamate, moderate concentrations of NaCl, Zn2+, and Ca2+ and at the isoelectric pH. The FUS RNA recognition motif (RRM) and zinc-finger (ZnF) domains are found to undergo cold denaturation above 0°C at a temperature that is determined by the conformational stability of the ZnF domain. Cold unfolding exposes buried nonpolar residues that can participate in LLPS-promoting hydrophobic interactions. Therefore, these findings constitute the first evidence that FUS globular domains may have an active role in LLPS under cold stress conditions and in the assembly of stress granules, providing further insight into the environmental regulation of LLPS.DQ - Departamento de QuímicaUCIBIO - Applied Molecular Biosciences UnitRUNFélix, Sara S.Laurents, Douglas V.Oroz, JavierCabrita, Eurico J.2023-03-17T22:32:28Z2023-012023-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article13application/pdfhttp://hdl.handle.net/10362/150809eng0961-8368PURE: 56249122https://doi.org/10.1002/pro.4521info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:33:15Zoai:run.unl.pt:10362/150809Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:54:20.170252Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Fused in sarcoma undergoes cold denaturation
Implications for phase separation
title Fused in sarcoma undergoes cold denaturation
spellingShingle Fused in sarcoma undergoes cold denaturation
Félix, Sara S.
cold denaturation
cold stress
fused in sarcoma (FUS)
liquid–liquid phase separation (LLPS)
nuclear magnetic resonance (NMR)
Biochemistry
Molecular Biology
title_short Fused in sarcoma undergoes cold denaturation
title_full Fused in sarcoma undergoes cold denaturation
title_fullStr Fused in sarcoma undergoes cold denaturation
title_full_unstemmed Fused in sarcoma undergoes cold denaturation
title_sort Fused in sarcoma undergoes cold denaturation
author Félix, Sara S.
author_facet Félix, Sara S.
Laurents, Douglas V.
Oroz, Javier
Cabrita, Eurico J.
author_role author
author2 Laurents, Douglas V.
Oroz, Javier
Cabrita, Eurico J.
author2_role author
author
author
dc.contributor.none.fl_str_mv DQ - Departamento de Química
UCIBIO - Applied Molecular Biosciences Unit
RUN
dc.contributor.author.fl_str_mv Félix, Sara S.
Laurents, Douglas V.
Oroz, Javier
Cabrita, Eurico J.
dc.subject.por.fl_str_mv cold denaturation
cold stress
fused in sarcoma (FUS)
liquid–liquid phase separation (LLPS)
nuclear magnetic resonance (NMR)
Biochemistry
Molecular Biology
topic cold denaturation
cold stress
fused in sarcoma (FUS)
liquid–liquid phase separation (LLPS)
nuclear magnetic resonance (NMR)
Biochemistry
Molecular Biology
description Funding Information: The authors would also like to acknowledge Prof. Dr. Jaime Mota, Dra. Irina Franco for the technical assistance with the microscopic experiments, Philip O'Toole for the aid in protein production and Dr. Aldino Viegas and Dr. David Pantoja-Uceda for the support and valuable discussions regarding NMR spectroscopy. The authors also thank FCT-Portugal for the PhD grant attributed to SF (PD/BD/148028/2019) under the PTNMRPhD Program. JO is a recipient of a Leonardo Grant from the Spanish BBVA Foundation (BBM_TRA_0203) and a Ramón y Cajal Grant (RYC2018-026042-I funded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future.”) JO and DVL are supported by the Spanish Grants PID-2019-109276RA-I00 and PID-2019-109306RB-I00, respectively, both funded by MCIN/AEI/10.13039/501100011033. The NMR spectrometers are part of the National NMR Facility supported by FCT-Portugal (ROTEIRO/0031/2013–PINFRA/22161/2016, co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). The 800 MHz spectrometer present in the “Manuel Rico” NMR laboratory (LMR-CSIC) is a node of the Spanish Large-Scale National Facility (ICTS R-LRB-MR). Publisher Copyright: © 2022 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.
publishDate 2023
dc.date.none.fl_str_mv 2023-03-17T22:32:28Z
2023-01
2023-01-01T00:00:00Z
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PURE: 56249122
https://doi.org/10.1002/pro.4521
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