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Intrinsically Disordered Proteins Display No Preference for Chaperone Binding In Vivo
Intrinsically disordered/unstructured proteins (IDPs) are extremely sensitive to proteolysis in vitro, but show no enhanced degradation rates in vivo. Their existence and functioning may be explained if IDPs are preferentially associated with chaperones in the cell, which may offer protection agains...
Autores principales: | , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265518/ https://www.ncbi.nlm.nih.gov/pubmed/18369417 http://dx.doi.org/10.1371/journal.pcbi.1000017 |
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author | Hegyi, Hedi Tompa, Peter |
author_facet | Hegyi, Hedi Tompa, Peter |
author_sort | Hegyi, Hedi |
collection | PubMed |
description | Intrinsically disordered/unstructured proteins (IDPs) are extremely sensitive to proteolysis in vitro, but show no enhanced degradation rates in vivo. Their existence and functioning may be explained if IDPs are preferentially associated with chaperones in the cell, which may offer protection against degradation by proteases. To test this inference, we took pairwise interaction data from high-throughput interaction studies and analyzed to see if predicted disorder correlates with the tendency of chaperone binding by proteins. Our major finding is that disorder predicted by the IUPred algorithm actually shows negative correlation with chaperone binding in E. coli, S. cerevisiae, and metazoa species. Since predicted disorder positively correlates with the tendency of partner binding in the interactome, the difference between the disorder of chaperone-binding and non-binding proteins is even more pronounced if normalized to their overall tendency to be involved in pairwise protein–protein interactions. We argue that chaperone binding is primarily required for folding of globular proteins, as reflected in an increased preference for chaperones of proteins in which at least one Pfam domain exists. In terms of the functional consequences of chaperone binding of mostly disordered proteins, we suggest that its primary reason is not the assistance of folding, but promotion of assembly with partners. In support of this conclusion, we show that IDPs that bind chaperones also tend to bind other proteins. |
format | Text |
id | pubmed-2265518 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-22655182008-03-08 Intrinsically Disordered Proteins Display No Preference for Chaperone Binding In Vivo Hegyi, Hedi Tompa, Peter PLoS Comput Biol Research Article Intrinsically disordered/unstructured proteins (IDPs) are extremely sensitive to proteolysis in vitro, but show no enhanced degradation rates in vivo. Their existence and functioning may be explained if IDPs are preferentially associated with chaperones in the cell, which may offer protection against degradation by proteases. To test this inference, we took pairwise interaction data from high-throughput interaction studies and analyzed to see if predicted disorder correlates with the tendency of chaperone binding by proteins. Our major finding is that disorder predicted by the IUPred algorithm actually shows negative correlation with chaperone binding in E. coli, S. cerevisiae, and metazoa species. Since predicted disorder positively correlates with the tendency of partner binding in the interactome, the difference between the disorder of chaperone-binding and non-binding proteins is even more pronounced if normalized to their overall tendency to be involved in pairwise protein–protein interactions. We argue that chaperone binding is primarily required for folding of globular proteins, as reflected in an increased preference for chaperones of proteins in which at least one Pfam domain exists. In terms of the functional consequences of chaperone binding of mostly disordered proteins, we suggest that its primary reason is not the assistance of folding, but promotion of assembly with partners. In support of this conclusion, we show that IDPs that bind chaperones also tend to bind other proteins. Public Library of Science 2008-03-07 /pmc/articles/PMC2265518/ /pubmed/18369417 http://dx.doi.org/10.1371/journal.pcbi.1000017 Text en Hegyi and Tompa. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Hegyi, Hedi Tompa, Peter Intrinsically Disordered Proteins Display No Preference for Chaperone Binding In Vivo |
title | Intrinsically Disordered Proteins Display No Preference for Chaperone Binding In Vivo |
title_full | Intrinsically Disordered Proteins Display No Preference for Chaperone Binding In Vivo |
title_fullStr | Intrinsically Disordered Proteins Display No Preference for Chaperone Binding In Vivo |
title_full_unstemmed | Intrinsically Disordered Proteins Display No Preference for Chaperone Binding In Vivo |
title_short | Intrinsically Disordered Proteins Display No Preference for Chaperone Binding In Vivo |
title_sort | intrinsically disordered proteins display no preference for chaperone binding in vivo |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265518/ https://www.ncbi.nlm.nih.gov/pubmed/18369417 http://dx.doi.org/10.1371/journal.pcbi.1000017 |
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