Characterization of design grammar of peptides for regulating liquid droplets and aggregates of FUS

Abstract Liquid droplets of aggregation-prone proteins, which become hydrogels or form amyloid fibrils, are a potential target for drug discovery. In this study, we proposed an experiment-guided protocol for characterizing the design grammar of peptides that can regulate droplet formation and aggreg...

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Autores principales:	Kiyoto Kamagata, Rika Chiba, Ichiro Kawahata, Nanako Iwaki, Saori Kanbayashi, Kana Maeda, Hiroto Takahashi, Atsushi Hirano, Koji Fukunaga, Keisuke Ikeda, Tomoshi Kameda
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5c28b549012a45df95489b66f2315847
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spelling	oai:doaj.org-article:5c28b549012a45df95489b66f23158472021-12-02T11:45:01ZCharacterization of design grammar of peptides for regulating liquid droplets and aggregates of FUS10.1038/s41598-021-86098-12045-2322https://doaj.org/article/5c28b549012a45df95489b66f23158472021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86098-1https://doaj.org/toc/2045-2322Abstract Liquid droplets of aggregation-prone proteins, which become hydrogels or form amyloid fibrils, are a potential target for drug discovery. In this study, we proposed an experiment-guided protocol for characterizing the design grammar of peptides that can regulate droplet formation and aggregation. The protocol essentially involves investigation of 19 amino acid additives and polymerization of the identified amino acids. As a proof of concept, we applied this protocol to fused in sarcoma (FUS). First, we evaluated 19 amino acid additives for an FUS solution and identified Arg and Tyr as suppressors of droplet formation. Molecular dynamics simulations suggested that the Arg additive interacts with specific residues of FUS, thereby inhibiting the cation–π and electrostatic interactions between the FUS molecules. Second, we observed that Arg polymers promote FUS droplet formation, unlike Arg monomers, by bridging the FUS molecules. Third, we found that the Arg additive suppressed solid aggregate formation of FUS, while Arg polymer enhanced it. Finally, we observed that amyloid-forming peptides induced the conversion of FUS droplets to solid aggregates of FUS. The developed protocol could be used for the primary design of peptides controlling liquid droplets and aggregates of proteins.Kiyoto KamagataRika ChibaIchiro KawahataNanako IwakiSaori KanbayashiKana MaedaHiroto TakahashiAtsushi HiranoKoji FukunagaKeisuke IkedaTomoshi KamedaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kiyoto Kamagata Rika Chiba Ichiro Kawahata Nanako Iwaki Saori Kanbayashi Kana Maeda Hiroto Takahashi Atsushi Hirano Koji Fukunaga Keisuke Ikeda Tomoshi Kameda Characterization of design grammar of peptides for regulating liquid droplets and aggregates of FUS
description	Abstract Liquid droplets of aggregation-prone proteins, which become hydrogels or form amyloid fibrils, are a potential target for drug discovery. In this study, we proposed an experiment-guided protocol for characterizing the design grammar of peptides that can regulate droplet formation and aggregation. The protocol essentially involves investigation of 19 amino acid additives and polymerization of the identified amino acids. As a proof of concept, we applied this protocol to fused in sarcoma (FUS). First, we evaluated 19 amino acid additives for an FUS solution and identified Arg and Tyr as suppressors of droplet formation. Molecular dynamics simulations suggested that the Arg additive interacts with specific residues of FUS, thereby inhibiting the cation–π and electrostatic interactions between the FUS molecules. Second, we observed that Arg polymers promote FUS droplet formation, unlike Arg monomers, by bridging the FUS molecules. Third, we found that the Arg additive suppressed solid aggregate formation of FUS, while Arg polymer enhanced it. Finally, we observed that amyloid-forming peptides induced the conversion of FUS droplets to solid aggregates of FUS. The developed protocol could be used for the primary design of peptides controlling liquid droplets and aggregates of proteins.
format	article
author	Kiyoto Kamagata Rika Chiba Ichiro Kawahata Nanako Iwaki Saori Kanbayashi Kana Maeda Hiroto Takahashi Atsushi Hirano Koji Fukunaga Keisuke Ikeda Tomoshi Kameda
author_facet	Kiyoto Kamagata Rika Chiba Ichiro Kawahata Nanako Iwaki Saori Kanbayashi Kana Maeda Hiroto Takahashi Atsushi Hirano Koji Fukunaga Keisuke Ikeda Tomoshi Kameda
author_sort	Kiyoto Kamagata
title	Characterization of design grammar of peptides for regulating liquid droplets and aggregates of FUS
title_short	Characterization of design grammar of peptides for regulating liquid droplets and aggregates of FUS
title_full	Characterization of design grammar of peptides for regulating liquid droplets and aggregates of FUS
title_fullStr	Characterization of design grammar of peptides for regulating liquid droplets and aggregates of FUS
title_full_unstemmed	Characterization of design grammar of peptides for regulating liquid droplets and aggregates of FUS
title_sort	characterization of design grammar of peptides for regulating liquid droplets and aggregates of fus
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5c28b549012a45df95489b66f2315847
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Characterization of design grammar of peptides for regulating liquid droplets and aggregates of FUS

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