Mutation-driven evolution of antibacterial function in an ancestral antifungal scaffold: Significance for peptide engineering
Mutation-driven evolution of novel function on an old gene has been documented in many development- and adaptive immunity-related genes but is poorly understood in immune effector molecules. Drosomycin-type antifungal peptides (DTAFPs) are a family of defensin-type effectors found in plants and ecdy...
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.1053078/full |
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| author | Jing Gu Noriyoshi Isozumi Bin Gao Shinya Ohki Shunyi Zhu |
| author_facet | Jing Gu Noriyoshi Isozumi Bin Gao Shinya Ohki Shunyi Zhu |
| author_sort | Jing Gu |
| collection | DOAJ |
| description | Mutation-driven evolution of novel function on an old gene has been documented in many development- and adaptive immunity-related genes but is poorly understood in immune effector molecules. Drosomycin-type antifungal peptides (DTAFPs) are a family of defensin-type effectors found in plants and ecdysozoans. Their primitive function was to control fungal infection and then co-opted for fighting against bacterial infection in plants, insects, and nematodes. This provides a model to study the structural and evolutionary mechanisms behind such functional diversification. In the present study, we determined the solution structure of mehamycin, a DTAFP from the Northern root-knot nematode Meloidogyne hapla with antibacterial activity and an 18-mer insert, and studied the mutational effect through using a mutant with the insert deleted. Mehamycin adopts an expected cysteine-stabilized α-helix and β-sheet fold in its core scaffold and the inserted region, called single Disulfide Bridge-linked Domain (abbreviated as sDBD), forms an extended loop protruding from the scaffold. The latter folds into an amphipathic architecture stabilized by one disulfide bridge, which likely confers mehamycin a bacterial membrane permeability. Deletion of the sDBD remarkably decreased the ability but accompanying an increase in thermostability, indicative of a structure-function trade-off in the mehamycin evolution. Allosteric analysis revealed an interior interaction between the two domains, which might promote point mutations at some key sites of the core domain and ultimately give rise to the emergence of antibacterial function. Our work may be valuable in guiding protein engineering of mehamycin to improve its activity and stability. |
| first_indexed | 2024-04-13T13:24:24Z |
| format | Article |
| id | doaj.art-e963811f24b0432b8122578161a3b774 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-13T13:24:24Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Microbiology |
| spelling | doaj.art-e963811f24b0432b8122578161a3b7742022-12-22T02:45:13ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-12-011310.3389/fmicb.2022.10530781053078Mutation-driven evolution of antibacterial function in an ancestral antifungal scaffold: Significance for peptide engineeringJing Gu0Noriyoshi Isozumi1Bin Gao2Shinya Ohki3Shunyi Zhu4Group of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, ChinaCenter for Nano Materials and Technology (CNMT), Japan Advanced Institute of Science and Technology (JAIST), Nomi, Ishikawa, JapanGroup of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, ChinaCenter for Nano Materials and Technology (CNMT), Japan Advanced Institute of Science and Technology (JAIST), Nomi, Ishikawa, JapanGroup of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, ChinaMutation-driven evolution of novel function on an old gene has been documented in many development- and adaptive immunity-related genes but is poorly understood in immune effector molecules. Drosomycin-type antifungal peptides (DTAFPs) are a family of defensin-type effectors found in plants and ecdysozoans. Their primitive function was to control fungal infection and then co-opted for fighting against bacterial infection in plants, insects, and nematodes. This provides a model to study the structural and evolutionary mechanisms behind such functional diversification. In the present study, we determined the solution structure of mehamycin, a DTAFP from the Northern root-knot nematode Meloidogyne hapla with antibacterial activity and an 18-mer insert, and studied the mutational effect through using a mutant with the insert deleted. Mehamycin adopts an expected cysteine-stabilized α-helix and β-sheet fold in its core scaffold and the inserted region, called single Disulfide Bridge-linked Domain (abbreviated as sDBD), forms an extended loop protruding from the scaffold. The latter folds into an amphipathic architecture stabilized by one disulfide bridge, which likely confers mehamycin a bacterial membrane permeability. Deletion of the sDBD remarkably decreased the ability but accompanying an increase in thermostability, indicative of a structure-function trade-off in the mehamycin evolution. Allosteric analysis revealed an interior interaction between the two domains, which might promote point mutations at some key sites of the core domain and ultimately give rise to the emergence of antibacterial function. Our work may be valuable in guiding protein engineering of mehamycin to improve its activity and stability.https://www.frontiersin.org/articles/10.3389/fmicb.2022.1053078/fulldrosomycinmehamycinnematodeco-optionallosterydeletion mutant |
| spellingShingle | Jing Gu Noriyoshi Isozumi Bin Gao Shinya Ohki Shunyi Zhu Mutation-driven evolution of antibacterial function in an ancestral antifungal scaffold: Significance for peptide engineering Frontiers in Microbiology drosomycin mehamycin nematode co-option allostery deletion mutant |
| title | Mutation-driven evolution of antibacterial function in an ancestral antifungal scaffold: Significance for peptide engineering |
| title_full | Mutation-driven evolution of antibacterial function in an ancestral antifungal scaffold: Significance for peptide engineering |
| title_fullStr | Mutation-driven evolution of antibacterial function in an ancestral antifungal scaffold: Significance for peptide engineering |
| title_full_unstemmed | Mutation-driven evolution of antibacterial function in an ancestral antifungal scaffold: Significance for peptide engineering |
| title_short | Mutation-driven evolution of antibacterial function in an ancestral antifungal scaffold: Significance for peptide engineering |
| title_sort | mutation driven evolution of antibacterial function in an ancestral antifungal scaffold significance for peptide engineering |
| topic | drosomycin mehamycin nematode co-option allostery deletion mutant |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.1053078/full |
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