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Molecular Determinants of Selectivity in Disordered Complexes May Shed Light on Specificity in Protein Condensates
Biomolecular condensates challenge the classical concepts of molecular recognition. The variable composition and heterogeneous conformations of liquid-like protein droplets are bottlenecks for high-resolution structural studies. To obtain atomistic insights into the organization of these assemblies,...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773858/ https://www.ncbi.nlm.nih.gov/pubmed/35053240 http://dx.doi.org/10.3390/biom12010092 |
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author | Monzon, Alexander Miguel Piovesan, Damiano Fuxreiter, Monika |
author_facet | Monzon, Alexander Miguel Piovesan, Damiano Fuxreiter, Monika |
author_sort | Monzon, Alexander Miguel |
collection | PubMed |
description | Biomolecular condensates challenge the classical concepts of molecular recognition. The variable composition and heterogeneous conformations of liquid-like protein droplets are bottlenecks for high-resolution structural studies. To obtain atomistic insights into the organization of these assemblies, here we have characterized the conformational ensembles of specific disordered complexes, including those of droplet-driving proteins. First, we found that these specific complexes exhibit a high degree of conformational heterogeneity. Second, we found that residues forming contacts at the interface also sample many conformations. Third, we found that different patterns of contacting residues form the specific interface. In addition, we observed a wide range of sequence motifs mediating disordered interactions, including charged, hydrophobic and polar contacts. These results demonstrate that selective recognition can be realized by variable patterns of weakly defined interaction motifs in many different binding configurations. We propose that these principles also play roles in determining the selectivity of biomolecular condensates. |
format | Online Article Text |
id | pubmed-8773858 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87738582022-01-21 Molecular Determinants of Selectivity in Disordered Complexes May Shed Light on Specificity in Protein Condensates Monzon, Alexander Miguel Piovesan, Damiano Fuxreiter, Monika Biomolecules Article Biomolecular condensates challenge the classical concepts of molecular recognition. The variable composition and heterogeneous conformations of liquid-like protein droplets are bottlenecks for high-resolution structural studies. To obtain atomistic insights into the organization of these assemblies, here we have characterized the conformational ensembles of specific disordered complexes, including those of droplet-driving proteins. First, we found that these specific complexes exhibit a high degree of conformational heterogeneity. Second, we found that residues forming contacts at the interface also sample many conformations. Third, we found that different patterns of contacting residues form the specific interface. In addition, we observed a wide range of sequence motifs mediating disordered interactions, including charged, hydrophobic and polar contacts. These results demonstrate that selective recognition can be realized by variable patterns of weakly defined interaction motifs in many different binding configurations. We propose that these principles also play roles in determining the selectivity of biomolecular condensates. MDPI 2022-01-06 /pmc/articles/PMC8773858/ /pubmed/35053240 http://dx.doi.org/10.3390/biom12010092 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Monzon, Alexander Miguel Piovesan, Damiano Fuxreiter, Monika Molecular Determinants of Selectivity in Disordered Complexes May Shed Light on Specificity in Protein Condensates |
title | Molecular Determinants of Selectivity in Disordered Complexes May Shed Light on Specificity in Protein Condensates |
title_full | Molecular Determinants of Selectivity in Disordered Complexes May Shed Light on Specificity in Protein Condensates |
title_fullStr | Molecular Determinants of Selectivity in Disordered Complexes May Shed Light on Specificity in Protein Condensates |
title_full_unstemmed | Molecular Determinants of Selectivity in Disordered Complexes May Shed Light on Specificity in Protein Condensates |
title_short | Molecular Determinants of Selectivity in Disordered Complexes May Shed Light on Specificity in Protein Condensates |
title_sort | molecular determinants of selectivity in disordered complexes may shed light on specificity in protein condensates |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773858/ https://www.ncbi.nlm.nih.gov/pubmed/35053240 http://dx.doi.org/10.3390/biom12010092 |
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