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Phase separation driven by interchangeable properties in the intrinsically disordered regions of protein paralogs

Paralogs, arising from gene duplications, increase the functional diversity of proteins. Protein functions in paralog families have been extensively studied, but little is known about the roles that intrinsically disordered regions (IDRs) play in their paralogs. Without a folded structure to restrai...

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Autores principales: Chiu, Shih-Hui, Ho, Wen-Lin, Sun, Yung-Chen, Kuo, Jean-Cheng, Huang, Jie-rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9054762/
https://www.ncbi.nlm.nih.gov/pubmed/35487971
http://dx.doi.org/10.1038/s42003-022-03354-4
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author Chiu, Shih-Hui
Ho, Wen-Lin
Sun, Yung-Chen
Kuo, Jean-Cheng
Huang, Jie-rong
author_facet Chiu, Shih-Hui
Ho, Wen-Lin
Sun, Yung-Chen
Kuo, Jean-Cheng
Huang, Jie-rong
author_sort Chiu, Shih-Hui
collection PubMed
description Paralogs, arising from gene duplications, increase the functional diversity of proteins. Protein functions in paralog families have been extensively studied, but little is known about the roles that intrinsically disordered regions (IDRs) play in their paralogs. Without a folded structure to restrain them, IDRs mutate more diversely along with evolution. However, how the diversity of IDRs in a paralog family affects their functions is unexplored. Using the RNA-binding protein Musashi family as an example, we applied multiple structural techniques and phylogenetic analysis to show how members in a paralog family have evolved their IDRs to different physicochemical properties but converge to the same function. In this example, the lower prion-like tendency of Musashi-1’s IDRs, rather than Musashi-2’s, is compensated by its higher α-helical propensity to assist their assembly. Our work suggests that, no matter how diverse they become, IDRs could evolve different traits to a converged function, such as liquid-liquid phase separation.
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spelling pubmed-90547622022-05-01 Phase separation driven by interchangeable properties in the intrinsically disordered regions of protein paralogs Chiu, Shih-Hui Ho, Wen-Lin Sun, Yung-Chen Kuo, Jean-Cheng Huang, Jie-rong Commun Biol Article Paralogs, arising from gene duplications, increase the functional diversity of proteins. Protein functions in paralog families have been extensively studied, but little is known about the roles that intrinsically disordered regions (IDRs) play in their paralogs. Without a folded structure to restrain them, IDRs mutate more diversely along with evolution. However, how the diversity of IDRs in a paralog family affects their functions is unexplored. Using the RNA-binding protein Musashi family as an example, we applied multiple structural techniques and phylogenetic analysis to show how members in a paralog family have evolved their IDRs to different physicochemical properties but converge to the same function. In this example, the lower prion-like tendency of Musashi-1’s IDRs, rather than Musashi-2’s, is compensated by its higher α-helical propensity to assist their assembly. Our work suggests that, no matter how diverse they become, IDRs could evolve different traits to a converged function, such as liquid-liquid phase separation. Nature Publishing Group UK 2022-04-29 /pmc/articles/PMC9054762/ /pubmed/35487971 http://dx.doi.org/10.1038/s42003-022-03354-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Chiu, Shih-Hui
Ho, Wen-Lin
Sun, Yung-Chen
Kuo, Jean-Cheng
Huang, Jie-rong
Phase separation driven by interchangeable properties in the intrinsically disordered regions of protein paralogs
title Phase separation driven by interchangeable properties in the intrinsically disordered regions of protein paralogs
title_full Phase separation driven by interchangeable properties in the intrinsically disordered regions of protein paralogs
title_fullStr Phase separation driven by interchangeable properties in the intrinsically disordered regions of protein paralogs
title_full_unstemmed Phase separation driven by interchangeable properties in the intrinsically disordered regions of protein paralogs
title_short Phase separation driven by interchangeable properties in the intrinsically disordered regions of protein paralogs
title_sort phase separation driven by interchangeable properties in the intrinsically disordered regions of protein paralogs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9054762/
https://www.ncbi.nlm.nih.gov/pubmed/35487971
http://dx.doi.org/10.1038/s42003-022-03354-4
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