The role of non-native interactions in the folding of knotted proteins.
Stochastic simulations of coarse-grained protein models are used to investigate the propensity to form knots in early stages of protein folding. The study is carried out comparatively for two homologous carbamoyltransferases, a natively-knotted N-acetylornithine carbamoyltransferase (AOTCase) and an...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC3375218?pdf=render |
| _version_ | 1818180363251351552 |
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| author | Tatjana Skrbić Cristian Micheletti Pietro Faccioli |
| author_facet | Tatjana Skrbić Cristian Micheletti Pietro Faccioli |
| author_sort | Tatjana Skrbić |
| collection | DOAJ |
| description | Stochastic simulations of coarse-grained protein models are used to investigate the propensity to form knots in early stages of protein folding. The study is carried out comparatively for two homologous carbamoyltransferases, a natively-knotted N-acetylornithine carbamoyltransferase (AOTCase) and an unknotted ornithine carbamoyltransferase (OTCase). In addition, two different sets of pairwise amino acid interactions are considered: one promoting exclusively native interactions, and the other additionally including non-native quasi-chemical and electrostatic interactions. With the former model neither protein shows a propensity to form knots. With the additional non-native interactions, knotting propensity remains negligible for the natively-unknotted OTCase while for AOTCase it is much enhanced. Analysis of the trajectories suggests that the different entanglement of the two transcarbamylases follows from the tendency of the C-terminal to point away from (for OTCase) or approach and eventually thread (for AOTCase) other regions of partly-folded protein. The analysis of the OTCase/AOTCase pair clarifies that natively-knotted proteins can spontaneously knot during early folding stages and that non-native sequence-dependent interactions are important for promoting and disfavouring early knotting events. |
| first_indexed | 2024-12-11T21:18:35Z |
| format | Article |
| id | doaj.art-de2c56f85a5a498f80fef32bb046e5da |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-11T21:18:35Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-de2c56f85a5a498f80fef32bb046e5da2022-12-22T00:50:32ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582012-01-0186e100250410.1371/journal.pcbi.1002504The role of non-native interactions in the folding of knotted proteins.Tatjana SkrbićCristian MichelettiPietro FaccioliStochastic simulations of coarse-grained protein models are used to investigate the propensity to form knots in early stages of protein folding. The study is carried out comparatively for two homologous carbamoyltransferases, a natively-knotted N-acetylornithine carbamoyltransferase (AOTCase) and an unknotted ornithine carbamoyltransferase (OTCase). In addition, two different sets of pairwise amino acid interactions are considered: one promoting exclusively native interactions, and the other additionally including non-native quasi-chemical and electrostatic interactions. With the former model neither protein shows a propensity to form knots. With the additional non-native interactions, knotting propensity remains negligible for the natively-unknotted OTCase while for AOTCase it is much enhanced. Analysis of the trajectories suggests that the different entanglement of the two transcarbamylases follows from the tendency of the C-terminal to point away from (for OTCase) or approach and eventually thread (for AOTCase) other regions of partly-folded protein. The analysis of the OTCase/AOTCase pair clarifies that natively-knotted proteins can spontaneously knot during early folding stages and that non-native sequence-dependent interactions are important for promoting and disfavouring early knotting events.http://europepmc.org/articles/PMC3375218?pdf=render |
| spellingShingle | Tatjana Skrbić Cristian Micheletti Pietro Faccioli The role of non-native interactions in the folding of knotted proteins. PLoS Computational Biology |
| title | The role of non-native interactions in the folding of knotted proteins. |
| title_full | The role of non-native interactions in the folding of knotted proteins. |
| title_fullStr | The role of non-native interactions in the folding of knotted proteins. |
| title_full_unstemmed | The role of non-native interactions in the folding of knotted proteins. |
| title_short | The role of non-native interactions in the folding of knotted proteins. |
| title_sort | role of non native interactions in the folding of knotted proteins |
| url | http://europepmc.org/articles/PMC3375218?pdf=render |
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