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Uncovering the molecular mechanism for dual effect of ATP on phase separation in FUS solution

Recent studies reported that adenosine triphosphate (ATP) could inhibit and enhance the phase separation in prion-like proteins. The molecular mechanism underlying such a puzzling phenomenon remains elusive. Here, taking the fused in sarcoma (FUS) solution as an example, we comprehensively reveal th...

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Autores principales: Ren, Chun-Lai, Shan, Yue, Zhang, Pengfei, Ding, Hong-Ming, Ma, Yu-Qiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9473584/
https://www.ncbi.nlm.nih.gov/pubmed/36103543
http://dx.doi.org/10.1126/sciadv.abo7885
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author Ren, Chun-Lai
Shan, Yue
Zhang, Pengfei
Ding, Hong-Ming
Ma, Yu-Qiang
author_facet Ren, Chun-Lai
Shan, Yue
Zhang, Pengfei
Ding, Hong-Ming
Ma, Yu-Qiang
author_sort Ren, Chun-Lai
collection PubMed
description Recent studies reported that adenosine triphosphate (ATP) could inhibit and enhance the phase separation in prion-like proteins. The molecular mechanism underlying such a puzzling phenomenon remains elusive. Here, taking the fused in sarcoma (FUS) solution as an example, we comprehensively reveal the underlying mechanism by which ATP regulates phase separation by combining the semiempirical quantum mechanical method, mean-field theory, and molecular simulation. At the microscopic level, ATP acts as a bivalent or trivalent binder; at the macroscopic level, the reentrant phase separation occurs in dilute FUS solutions, resulting from the ATP concentration–dependent binding ability under different conditions. The ATP concentration for dissolving the protein condensates is about 10 mM, agreeing with experimental results. Furthermore, from a dynamic point of view, the effect of ATP on phase separation is also nonmonotonic. This work provides a clear physical description of the microscopic interaction and macroscopic phase diagram of the ATP-modulated phase separation.
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spelling pubmed-94735842022-09-29 Uncovering the molecular mechanism for dual effect of ATP on phase separation in FUS solution Ren, Chun-Lai Shan, Yue Zhang, Pengfei Ding, Hong-Ming Ma, Yu-Qiang Sci Adv Physical and Materials Sciences Recent studies reported that adenosine triphosphate (ATP) could inhibit and enhance the phase separation in prion-like proteins. The molecular mechanism underlying such a puzzling phenomenon remains elusive. Here, taking the fused in sarcoma (FUS) solution as an example, we comprehensively reveal the underlying mechanism by which ATP regulates phase separation by combining the semiempirical quantum mechanical method, mean-field theory, and molecular simulation. At the microscopic level, ATP acts as a bivalent or trivalent binder; at the macroscopic level, the reentrant phase separation occurs in dilute FUS solutions, resulting from the ATP concentration–dependent binding ability under different conditions. The ATP concentration for dissolving the protein condensates is about 10 mM, agreeing with experimental results. Furthermore, from a dynamic point of view, the effect of ATP on phase separation is also nonmonotonic. This work provides a clear physical description of the microscopic interaction and macroscopic phase diagram of the ATP-modulated phase separation. American Association for the Advancement of Science 2022-09-14 /pmc/articles/PMC9473584/ /pubmed/36103543 http://dx.doi.org/10.1126/sciadv.abo7885 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Physical and Materials Sciences
Ren, Chun-Lai
Shan, Yue
Zhang, Pengfei
Ding, Hong-Ming
Ma, Yu-Qiang
Uncovering the molecular mechanism for dual effect of ATP on phase separation in FUS solution
title Uncovering the molecular mechanism for dual effect of ATP on phase separation in FUS solution
title_full Uncovering the molecular mechanism for dual effect of ATP on phase separation in FUS solution
title_fullStr Uncovering the molecular mechanism for dual effect of ATP on phase separation in FUS solution
title_full_unstemmed Uncovering the molecular mechanism for dual effect of ATP on phase separation in FUS solution
title_short Uncovering the molecular mechanism for dual effect of ATP on phase separation in FUS solution
title_sort uncovering the molecular mechanism for dual effect of atp on phase separation in fus solution
topic Physical and Materials Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9473584/
https://www.ncbi.nlm.nih.gov/pubmed/36103543
http://dx.doi.org/10.1126/sciadv.abo7885
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