Neuromodulators as Interdomain Signaling Molecules Capable of Occupying Effector Binding Sites in Bacterial Transcription Factors
Hormones and neurotransmitters are important components of inter-kingdom signaling systems that ensure the coexistence of eukaryotes with their microbial community. Their ability to affect bacterial physiology, metabolism, and gene expression was evidenced by various experimental approaches, but dir...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/21/15863 |
| _version_ | 1797631812697063424 |
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| author | Yuri A. Purtov Olga N. Ozoline |
| author_facet | Yuri A. Purtov Olga N. Ozoline |
| author_sort | Yuri A. Purtov |
| collection | DOAJ |
| description | Hormones and neurotransmitters are important components of inter-kingdom signaling systems that ensure the coexistence of eukaryotes with their microbial community. Their ability to affect bacterial physiology, metabolism, and gene expression was evidenced by various experimental approaches, but direct penetration into bacteria has only recently been reported. This opened the possibility of considering neuromodulators as potential effectors of bacterial ligand-dependent regulatory proteins. Here, we assessed the validity of this assumption for the neurotransmitters epinephrine, dopamine, and norepinephrine and two hormones (melatonin and serotonin). Using flexible molecular docking for transcription factors with ligand-dependent activity, we assessed the ability of neuromodulators to occupy their effector binding sites. For many transcription factors, including the global regulator of carbohydrate metabolism, CRP, and the key regulator of lactose assimilation, LacI, this ability was predicted based on the analysis of several 3D models. By occupying the ligand binding site, neuromodulators can sterically hinder the interaction of the target proteins with the natural effectors or even replace them. The data obtained suggest that the direct modulation of the activity of at least some bacterial transcriptional factors by neuromodulators is possible. Therefore, the natural hormonal background may be a factor that preadapts bacteria to the habitat through direct perception of host signaling molecules. |
| first_indexed | 2024-03-11T11:28:59Z |
| format | Article |
| id | doaj.art-ade92377ca8e421f80773b85c530b82f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T11:28:59Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ade92377ca8e421f80773b85c530b82f2023-11-10T15:05:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124211586310.3390/ijms242115863Neuromodulators as Interdomain Signaling Molecules Capable of Occupying Effector Binding Sites in Bacterial Transcription FactorsYuri A. Purtov0Olga N. Ozoline1Department of Functional Genomics of Prokaryotes, Institute of Cell Biophysics of the Russian Academy of Sciences, Federal Research Center Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Pushchino 142290, RussiaDepartment of Functional Genomics of Prokaryotes, Institute of Cell Biophysics of the Russian Academy of Sciences, Federal Research Center Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Pushchino 142290, RussiaHormones and neurotransmitters are important components of inter-kingdom signaling systems that ensure the coexistence of eukaryotes with their microbial community. Their ability to affect bacterial physiology, metabolism, and gene expression was evidenced by various experimental approaches, but direct penetration into bacteria has only recently been reported. This opened the possibility of considering neuromodulators as potential effectors of bacterial ligand-dependent regulatory proteins. Here, we assessed the validity of this assumption for the neurotransmitters epinephrine, dopamine, and norepinephrine and two hormones (melatonin and serotonin). Using flexible molecular docking for transcription factors with ligand-dependent activity, we assessed the ability of neuromodulators to occupy their effector binding sites. For many transcription factors, including the global regulator of carbohydrate metabolism, CRP, and the key regulator of lactose assimilation, LacI, this ability was predicted based on the analysis of several 3D models. By occupying the ligand binding site, neuromodulators can sterically hinder the interaction of the target proteins with the natural effectors or even replace them. The data obtained suggest that the direct modulation of the activity of at least some bacterial transcriptional factors by neuromodulators is possible. Therefore, the natural hormonal background may be a factor that preadapts bacteria to the habitat through direct perception of host signaling molecules.https://www.mdpi.com/1422-0067/24/21/15863neuromodulatorshormonesneurotransmittersmicrobiomestranscription factor–effector interactionflexible molecular docking |
| spellingShingle | Yuri A. Purtov Olga N. Ozoline Neuromodulators as Interdomain Signaling Molecules Capable of Occupying Effector Binding Sites in Bacterial Transcription Factors International Journal of Molecular Sciences neuromodulators hormones neurotransmitters microbiomes transcription factor–effector interaction flexible molecular docking |
| title | Neuromodulators as Interdomain Signaling Molecules Capable of Occupying Effector Binding Sites in Bacterial Transcription Factors |
| title_full | Neuromodulators as Interdomain Signaling Molecules Capable of Occupying Effector Binding Sites in Bacterial Transcription Factors |
| title_fullStr | Neuromodulators as Interdomain Signaling Molecules Capable of Occupying Effector Binding Sites in Bacterial Transcription Factors |
| title_full_unstemmed | Neuromodulators as Interdomain Signaling Molecules Capable of Occupying Effector Binding Sites in Bacterial Transcription Factors |
| title_short | Neuromodulators as Interdomain Signaling Molecules Capable of Occupying Effector Binding Sites in Bacterial Transcription Factors |
| title_sort | neuromodulators as interdomain signaling molecules capable of occupying effector binding sites in bacterial transcription factors |
| topic | neuromodulators hormones neurotransmitters microbiomes transcription factor–effector interaction flexible molecular docking |
| url | https://www.mdpi.com/1422-0067/24/21/15863 |
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