Identification of type VI secretion system effector-immunity pairs using structural bioinformatics.

Autor: Geller AM; Department of Plant Pathology and Microbiology, The Institute of Environmental Science, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel., Shalom M; Department of Plant Pathology and Microbiology, The Institute of Environmental Science, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel., Zlotkin D; Department of Plant Pathology and Microbiology, The Institute of Environmental Science, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel., Blum N; Department of Plant Pathology and Microbiology, The Institute of Environmental Science, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel., Levy A; Department of Plant Pathology and Microbiology, The Institute of Environmental Science, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel. alevy@mail.huji.ac.il.
Jazyk: angličtina
Zdroj: Molecular systems biology [Mol Syst Biol] 2024 Jun; Vol. 20 (6), pp. 702-718. Date of Electronic Publication: 2024 Apr 24.
DOI: 10.1038/s44320-024-00035-8
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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