Pervasive, conserved secondary structure in highly charged protein regions.
Understanding how protein sequences confer function remains a defining challenge in molecular biology. Two approaches have yielded enormous insight yet are often pursued separately: structure-based, where sequence-encoded structures mediate function, and disorder-based, where sequences dictate physi...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-10-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1011565&type=printable |
| _version_ | 1797311501742112768 |
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| author | Catherine G Triandafillou Rosalind Wenshan Pan Aaron R Dinner D Allan Drummond |
| author_facet | Catherine G Triandafillou Rosalind Wenshan Pan Aaron R Dinner D Allan Drummond |
| author_sort | Catherine G Triandafillou |
| collection | DOAJ |
| description | Understanding how protein sequences confer function remains a defining challenge in molecular biology. Two approaches have yielded enormous insight yet are often pursued separately: structure-based, where sequence-encoded structures mediate function, and disorder-based, where sequences dictate physicochemical and dynamical properties which determine function in the absence of stable structure. Here we study highly charged protein regions (>40% charged residues), which are routinely presumed to be disordered. Using recent advances in structure prediction and experimental structures, we show that roughly 40% of these regions form well-structured helices. Features often used to predict disorder-high charge density, low hydrophobicity, low sequence complexity, and evolutionarily varying length-are also compatible with solvated, variable-length helices. We show that a simple composition classifier predicts the existence of structure far better than well-established heuristics based on charge and hydropathy. We show that helical structure is more prevalent than previously appreciated in highly charged regions of diverse proteomes and characterize the conservation of highly charged regions. Our results underscore the importance of integrating, rather than choosing between, structure- and disorder-based approaches. |
| first_indexed | 2024-03-08T01:59:37Z |
| format | Article |
| id | doaj.art-40cc7b87a8974ed7808832dd547080a9 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-03-08T01:59:37Z |
| publishDate | 2023-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-40cc7b87a8974ed7808832dd547080a92024-02-14T05:31:26ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582023-10-011910e101156510.1371/journal.pcbi.1011565Pervasive, conserved secondary structure in highly charged protein regions.Catherine G TriandafillouRosalind Wenshan PanAaron R DinnerD Allan DrummondUnderstanding how protein sequences confer function remains a defining challenge in molecular biology. Two approaches have yielded enormous insight yet are often pursued separately: structure-based, where sequence-encoded structures mediate function, and disorder-based, where sequences dictate physicochemical and dynamical properties which determine function in the absence of stable structure. Here we study highly charged protein regions (>40% charged residues), which are routinely presumed to be disordered. Using recent advances in structure prediction and experimental structures, we show that roughly 40% of these regions form well-structured helices. Features often used to predict disorder-high charge density, low hydrophobicity, low sequence complexity, and evolutionarily varying length-are also compatible with solvated, variable-length helices. We show that a simple composition classifier predicts the existence of structure far better than well-established heuristics based on charge and hydropathy. We show that helical structure is more prevalent than previously appreciated in highly charged regions of diverse proteomes and characterize the conservation of highly charged regions. Our results underscore the importance of integrating, rather than choosing between, structure- and disorder-based approaches.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1011565&type=printable |
| spellingShingle | Catherine G Triandafillou Rosalind Wenshan Pan Aaron R Dinner D Allan Drummond Pervasive, conserved secondary structure in highly charged protein regions. PLoS Computational Biology |
| title | Pervasive, conserved secondary structure in highly charged protein regions. |
| title_full | Pervasive, conserved secondary structure in highly charged protein regions. |
| title_fullStr | Pervasive, conserved secondary structure in highly charged protein regions. |
| title_full_unstemmed | Pervasive, conserved secondary structure in highly charged protein regions. |
| title_short | Pervasive, conserved secondary structure in highly charged protein regions. |
| title_sort | pervasive conserved secondary structure in highly charged protein regions |
| url | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1011565&type=printable |
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