Investigating the trade-off between folding and function in a multidomain Y-family DNA polymerase
The way in which multidomain proteins fold has been a puzzling question for decades. Until now, the mechanisms and functions of domain interactions involved in multidomain protein folding have been obscure. Here, we develop structure-based models to investigate the folding and DNA-binding processes...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/60434 |
| _version_ | 1811202685557276672 |
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| author | Xiakun Chu Zucai Suo Jin Wang |
| author_facet | Xiakun Chu Zucai Suo Jin Wang |
| author_sort | Xiakun Chu |
| collection | DOAJ |
| description | The way in which multidomain proteins fold has been a puzzling question for decades. Until now, the mechanisms and functions of domain interactions involved in multidomain protein folding have been obscure. Here, we develop structure-based models to investigate the folding and DNA-binding processes of the multidomain Y-family DNA polymerase IV (DPO4). We uncover shifts in the folding mechanism among ordered domain-wise folding, backtracking folding, and cooperative folding, modulated by interdomain interactions. These lead to ‘U-shaped’ DPO4 folding kinetics. We characterize the effects of interdomain flexibility on the promotion of DPO4–DNA (un)binding, which probably contributes to the ability of DPO4 to bypass DNA lesions, which is a known biological role of Y-family polymerases. We suggest that the native topology of DPO4 leads to a trade-off between fast, stable folding and tight functional DNA binding. Our approach provides an effective way to quantitatively correlate the roles of protein interactions in conformational dynamics at the multidomain level. |
| first_indexed | 2024-04-12T02:42:42Z |
| format | Article |
| id | doaj.art-1a9f510a08d748fcb867d53a716829e8 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:42:42Z |
| publishDate | 2020-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-1a9f510a08d748fcb867d53a716829e82022-12-22T03:51:16ZengeLife Sciences Publications LtdeLife2050-084X2020-10-01910.7554/eLife.60434Investigating the trade-off between folding and function in a multidomain Y-family DNA polymeraseXiakun Chu0https://orcid.org/0000-0003-3166-7070Zucai Suo1https://orcid.org/0000-0003-3871-3420Jin Wang2https://orcid.org/0000-0002-2841-4913Department of Chemistry, State University of New York at Stony Brook, New York, United StatesDepartment of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, United StatesDepartment of Chemistry, State University of New York at Stony Brook, New York, United StatesThe way in which multidomain proteins fold has been a puzzling question for decades. Until now, the mechanisms and functions of domain interactions involved in multidomain protein folding have been obscure. Here, we develop structure-based models to investigate the folding and DNA-binding processes of the multidomain Y-family DNA polymerase IV (DPO4). We uncover shifts in the folding mechanism among ordered domain-wise folding, backtracking folding, and cooperative folding, modulated by interdomain interactions. These lead to ‘U-shaped’ DPO4 folding kinetics. We characterize the effects of interdomain flexibility on the promotion of DPO4–DNA (un)binding, which probably contributes to the ability of DPO4 to bypass DNA lesions, which is a known biological role of Y-family polymerases. We suggest that the native topology of DPO4 leads to a trade-off between fast, stable folding and tight functional DNA binding. Our approach provides an effective way to quantitatively correlate the roles of protein interactions in conformational dynamics at the multidomain level.https://elifesciences.org/articles/60434protein foldingenergy landscapeconformational dynamicsprotein-DNA recognitioncoarse-grained model |
| spellingShingle | Xiakun Chu Zucai Suo Jin Wang Investigating the trade-off between folding and function in a multidomain Y-family DNA polymerase eLife protein folding energy landscape conformational dynamics protein-DNA recognition coarse-grained model |
| title | Investigating the trade-off between folding and function in a multidomain Y-family DNA polymerase |
| title_full | Investigating the trade-off between folding and function in a multidomain Y-family DNA polymerase |
| title_fullStr | Investigating the trade-off between folding and function in a multidomain Y-family DNA polymerase |
| title_full_unstemmed | Investigating the trade-off between folding and function in a multidomain Y-family DNA polymerase |
| title_short | Investigating the trade-off between folding and function in a multidomain Y-family DNA polymerase |
| title_sort | investigating the trade off between folding and function in a multidomain y family dna polymerase |
| topic | protein folding energy landscape conformational dynamics protein-DNA recognition coarse-grained model |
| url | https://elifesciences.org/articles/60434 |
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