Identification of Homeobox Transcription Factors in a Dimorphic Fungus <i>Talaromyces marneffei</i> and Protein-Protein Interaction Prediction of RfeB
<i>Talaromyces marneffei</i> is a thermally dimorphic fungus that can cause life-threatening systemic mycoses, particularly in immunocompromised individuals. Fungal homeobox transcription factors control various developmental processes, including the regulation of sexual reproduction, mo...
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2024-09-01
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| author | Monsicha Pongpom Nopawit Khamto Panwarit Sukantamala Thitisuda Kalawil Tanaporn Wangsanut |
| author_facet | Monsicha Pongpom Nopawit Khamto Panwarit Sukantamala Thitisuda Kalawil Tanaporn Wangsanut |
| author_sort | Monsicha Pongpom |
| collection | DOAJ |
| description | <i>Talaromyces marneffei</i> is a thermally dimorphic fungus that can cause life-threatening systemic mycoses, particularly in immunocompromised individuals. Fungal homeobox transcription factors control various developmental processes, including the regulation of sexual reproduction, morphology, metabolism, and virulence. However, the function of homeobox proteins in <i>T. marneffei</i> has not been fully explored. Here, we searched the <i>T. marneffei</i> genome for the total homeobox transcription factors and predicted their biological relevance by performing gene expression analysis in different cell types, including conidia, mycelia, yeasts, and during phase transition. RfeB is selected for further computational analysis since (i) its transcripts were differentially expressed in different phases of <i>T. marneffei</i>, and (ii) this protein contains the highly conserved protein-protein interaction region (IR), which could be important for pathobiology and have therapeutic application. To assess the structure-function of the IR region, in silico alanine substitutions were performed at three-conserved IR residues (Asp276, Glu279, and Gln282) of RfeB, generating a triple RfeB mutated protein. Using 3D modeling and molecular dynamics simulations, we compared the protein complex formation of wild-type and mutated RfeB proteins with the putative partner candidate TmSwi5. Our results demonstrated that the mutated RfeB protein exhibited increased free binding energy, elevated protein compactness, and a reduced number of atomic contacts, suggesting disrupted protein stability and interaction. Notably, our model revealed that the IR residues primarily stabilized the RfeB binding sites located in the central region (CR). This computational approach for protein mutagenesis could provide a foundation for future experimental studies on the functional characterization of RfeB and other homeodomain-containing proteins in <i>T. marneffei</i>. |
| format | Article |
| id | doaj-art-9e198481b66f43dcae7c92fcfa616b62 |
| institution | OA Journals |
| issn | 2309-608X |
| language | English |
| publishDate | 2024-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj-art-9e198481b66f43dcae7c92fcfa616b622025-08-20T02:10:54ZengMDPI AGJournal of Fungi2309-608X2024-09-01101068710.3390/jof10100687Identification of Homeobox Transcription Factors in a Dimorphic Fungus <i>Talaromyces marneffei</i> and Protein-Protein Interaction Prediction of RfeBMonsicha Pongpom0Nopawit Khamto1Panwarit Sukantamala2Thitisuda Kalawil3Tanaporn Wangsanut4Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200, ThailandFaculty of Dentistry, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandDepartment of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand<i>Talaromyces marneffei</i> is a thermally dimorphic fungus that can cause life-threatening systemic mycoses, particularly in immunocompromised individuals. Fungal homeobox transcription factors control various developmental processes, including the regulation of sexual reproduction, morphology, metabolism, and virulence. However, the function of homeobox proteins in <i>T. marneffei</i> has not been fully explored. Here, we searched the <i>T. marneffei</i> genome for the total homeobox transcription factors and predicted their biological relevance by performing gene expression analysis in different cell types, including conidia, mycelia, yeasts, and during phase transition. RfeB is selected for further computational analysis since (i) its transcripts were differentially expressed in different phases of <i>T. marneffei</i>, and (ii) this protein contains the highly conserved protein-protein interaction region (IR), which could be important for pathobiology and have therapeutic application. To assess the structure-function of the IR region, in silico alanine substitutions were performed at three-conserved IR residues (Asp276, Glu279, and Gln282) of RfeB, generating a triple RfeB mutated protein. Using 3D modeling and molecular dynamics simulations, we compared the protein complex formation of wild-type and mutated RfeB proteins with the putative partner candidate TmSwi5. Our results demonstrated that the mutated RfeB protein exhibited increased free binding energy, elevated protein compactness, and a reduced number of atomic contacts, suggesting disrupted protein stability and interaction. Notably, our model revealed that the IR residues primarily stabilized the RfeB binding sites located in the central region (CR). This computational approach for protein mutagenesis could provide a foundation for future experimental studies on the functional characterization of RfeB and other homeodomain-containing proteins in <i>T. marneffei</i>.https://www.mdpi.com/2309-608X/10/10/687Hox proteinhomeoboxhomeodomainmolecular dynamics<i>Talaromyces marneffei</i>morphogenesis |
| spellingShingle | Monsicha Pongpom Nopawit Khamto Panwarit Sukantamala Thitisuda Kalawil Tanaporn Wangsanut Identification of Homeobox Transcription Factors in a Dimorphic Fungus <i>Talaromyces marneffei</i> and Protein-Protein Interaction Prediction of RfeB Journal of Fungi Hox protein homeobox homeodomain molecular dynamics <i>Talaromyces marneffei</i> morphogenesis |
| title | Identification of Homeobox Transcription Factors in a Dimorphic Fungus <i>Talaromyces marneffei</i> and Protein-Protein Interaction Prediction of RfeB |
| title_full | Identification of Homeobox Transcription Factors in a Dimorphic Fungus <i>Talaromyces marneffei</i> and Protein-Protein Interaction Prediction of RfeB |
| title_fullStr | Identification of Homeobox Transcription Factors in a Dimorphic Fungus <i>Talaromyces marneffei</i> and Protein-Protein Interaction Prediction of RfeB |
| title_full_unstemmed | Identification of Homeobox Transcription Factors in a Dimorphic Fungus <i>Talaromyces marneffei</i> and Protein-Protein Interaction Prediction of RfeB |
| title_short | Identification of Homeobox Transcription Factors in a Dimorphic Fungus <i>Talaromyces marneffei</i> and Protein-Protein Interaction Prediction of RfeB |
| title_sort | identification of homeobox transcription factors in a dimorphic fungus i talaromyces marneffei i and protein protein interaction prediction of rfeb |
| topic | Hox protein homeobox homeodomain molecular dynamics <i>Talaromyces marneffei</i> morphogenesis |
| url | https://www.mdpi.com/2309-608X/10/10/687 |
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