Academic Journal
Identification of type VI secretion system effector-immunity pairs using structural bioinformatics
| العنوان: | Identification of type VI secretion system effector-immunity pairs using structural bioinformatics |
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| المؤلفون: | Alexander M Geller, Maor Shalom, David Zlotkin, Noam Blum, Asaf Levy |
| المصدر: | Molecular Systems Biology, Vol 20, Iss 6, Pp 702-718 (2024) |
| بيانات النشر: | Springer Nature |
| سنة النشر: | 2024 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Alphafold-multimer, Effector-immunity Pairs, Foldseek, Structural Bioinformatics, Type VI Secretion System (T6SS), Biology (General), QH301-705.5, Medicine (General), R5-920 |
| الوصف: | The type VI secretion system (T6SS) is an important mediator of microbe–microbe and microbe–host interactions. Gram-negative bacteria use the T6SS to inject T6SS effectors (T6Es), which are usually proteins with toxic activity, into neighboring cells. Antibacterial effectors have cognate immunity proteins that neutralize self-intoxication. Here, we applied novel structural bioinformatic tools to perform systematic discovery and functional annotation of T6Es and their cognate immunity proteins from a dataset of 17,920 T6SS-encoding bacterial genomes. Using structural clustering, we identified 517 putative T6E families, outperforming sequence-based clustering. We developed a logistic regression model to reliably quantify protein–protein interaction of new T6E-immunity pairs, yielding candidate immunity proteins for 231 out of the 517 T6E families. We used sensitive structure-based annotation which yielded functional annotations for 51% of the T6E families, again outperforming sequence-based annotation. Next, we validated four novel T6E-immunity pairs using basic experiments in E. coli. In particular, we showed that the Pfam domain DUF3289 is a homolog of Colicin M and that DUF943 acts as its cognate immunity protein. Furthermore, we discovered a novel T6E that is a structural homolog of SleB, a lytic transglycosylase, and identified a specific glutamate that acts as its putative catalytic residue. Overall, this study applies novel structural bioinformatic tools to T6E-immunity pair discovery, and provides an extensive database of annotated T6E-immunity pairs. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1744-4292 |
| Relation: | https://doi.org/10.1038/s44320-024-00035-8; https://doaj.org/toc/1744-4292; https://doaj.org/article/698e146d4e66458daab7ee17e337220f |
| DOI: | 10.1038/s44320-024-00035-8 |
| الاتاحة: | https://doi.org/10.1038/s44320-024-00035-8 https://doaj.org/article/698e146d4e66458daab7ee17e337220f |
| رقم الانضمام: | edsbas.7ED1325F |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 17444292 |
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| DOI: | 10.1038/s44320-024-00035-8 |