Lambda CI Binding to Related Phage Operator Sequences Validates Alignment Algorithm and Highlights the Importance of Overlooked Bonds
Bacteriophage λ’s CI repressor protein controls a genetic switch between the virus’s lysogenic and lytic lifecycles, in part, by selectively binding to six different DNA sequences within the phage genome—collectively referred to as operator sites. However, the minimal level of information needed for...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/12/2221 |
| _version_ | 1797380884281688064 |
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| author | Jacklin Sedhom Lee A. Solomon |
| author_facet | Jacklin Sedhom Lee A. Solomon |
| author_sort | Jacklin Sedhom |
| collection | DOAJ |
| description | Bacteriophage λ’s CI repressor protein controls a genetic switch between the virus’s lysogenic and lytic lifecycles, in part, by selectively binding to six different DNA sequences within the phage genome—collectively referred to as operator sites. However, the minimal level of information needed for CI to recognize and specifically bind these six unique-but-related sequences is unclear. In a previous study, we introduced an algorithm that extracts the minimal direct readout information needed for λ-CI to recognize and bind its six binding sites. We further revealed direct readout information shared among three evolutionarily related lambdoid phages: λ-phage, Enterobacteria phage VT2-Sakai, and Stx2 converting phage I, suggesting that the λ-CI protein could bind to the operator sites of these other phages. In this study, we show that λ-CI can indeed bind the other two phages’ cognate binding sites as predicted using our algorithm, validating the hypotheses from that paper. We go on to demonstrate the importance of specific hydrogen bond donors and acceptors that are maintained despite changes to the nucleobase itself, and another that has an important role in recognition and binding. This in vitro validation of our algorithm supports its use as a tool to predict alternative binding sites for DNA-binding proteins. |
| first_indexed | 2024-03-08T20:43:27Z |
| format | Article |
| id | doaj.art-108f939e8a3d448f8b73f248a7c02911 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-08T20:43:27Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-108f939e8a3d448f8b73f248a7c029112023-12-22T14:11:23ZengMDPI AGGenes2073-44252023-12-011412222110.3390/genes14122221Lambda CI Binding to Related Phage Operator Sequences Validates Alignment Algorithm and Highlights the Importance of Overlooked BondsJacklin Sedhom0Lee A. Solomon1Department of Chemistry and Biochemistry, George Mason University, Fairfax, VA 22030, USADepartment of Chemistry and Biochemistry, George Mason University, Fairfax, VA 22030, USABacteriophage λ’s CI repressor protein controls a genetic switch between the virus’s lysogenic and lytic lifecycles, in part, by selectively binding to six different DNA sequences within the phage genome—collectively referred to as operator sites. However, the minimal level of information needed for CI to recognize and specifically bind these six unique-but-related sequences is unclear. In a previous study, we introduced an algorithm that extracts the minimal direct readout information needed for λ-CI to recognize and bind its six binding sites. We further revealed direct readout information shared among three evolutionarily related lambdoid phages: λ-phage, Enterobacteria phage VT2-Sakai, and Stx2 converting phage I, suggesting that the λ-CI protein could bind to the operator sites of these other phages. In this study, we show that λ-CI can indeed bind the other two phages’ cognate binding sites as predicted using our algorithm, validating the hypotheses from that paper. We go on to demonstrate the importance of specific hydrogen bond donors and acceptors that are maintained despite changes to the nucleobase itself, and another that has an important role in recognition and binding. This in vitro validation of our algorithm supports its use as a tool to predict alternative binding sites for DNA-binding proteins.https://www.mdpi.com/2073-4425/14/12/2221DNA-protein bindingbacteriophagegenetic regulationλ-phage |
| spellingShingle | Jacklin Sedhom Lee A. Solomon Lambda CI Binding to Related Phage Operator Sequences Validates Alignment Algorithm and Highlights the Importance of Overlooked Bonds Genes DNA-protein binding bacteriophage genetic regulation λ-phage |
| title | Lambda CI Binding to Related Phage Operator Sequences Validates Alignment Algorithm and Highlights the Importance of Overlooked Bonds |
| title_full | Lambda CI Binding to Related Phage Operator Sequences Validates Alignment Algorithm and Highlights the Importance of Overlooked Bonds |
| title_fullStr | Lambda CI Binding to Related Phage Operator Sequences Validates Alignment Algorithm and Highlights the Importance of Overlooked Bonds |
| title_full_unstemmed | Lambda CI Binding to Related Phage Operator Sequences Validates Alignment Algorithm and Highlights the Importance of Overlooked Bonds |
| title_short | Lambda CI Binding to Related Phage Operator Sequences Validates Alignment Algorithm and Highlights the Importance of Overlooked Bonds |
| title_sort | lambda ci binding to related phage operator sequences validates alignment algorithm and highlights the importance of overlooked bonds |
| topic | DNA-protein binding bacteriophage genetic regulation λ-phage |
| url | https://www.mdpi.com/2073-4425/14/12/2221 |
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