Molecular basis of type VI secretion system effector loading

Type VI secretion systems (T6SSs) are widespread bacterial nanomachines that deliver effectors into prokaryotic and eukaryotic cells. How an effector cargo is recruited and loaded into the Hcp ring assemblies that form the tube injected by the T6SS remains poorly understood. Pseudomonas aeruginosa has four T6SSs, each associated with a different Hcp protein. Here we use cryo-electron microscopy to resolve the structure of the Tce1 cargo loaded into a Hcp3 ring from the P. aeruginosa H3-T6SS. We show that a single Tce1 monomer interacts asymmetrically with, and is enclosed by, two hexameric Hcp3 rings, engaging key residues lining the inner surface of the Hcp3 disc. Our data indicate a stepwise loading mechanism, where an initial heterodimeric Hcp-cargo complex forms before ring encapsulation around the effector. Structural modelling suggests similar effector-Hcp3 interactions for a second T6SS effector, Tce2, which has antifungal activity. We propose that this mechanism enables coordinated delivery of a broad payload into target cells.

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Publication Details

Journal
Nature Microbiology
Published
2026-05-27
DOI
https://doi.org/10.1038/s41564-026-02363-x
Primary Topic
Vibrio bacteria research studies
Type
article
Field-Weighted Citation Impact
0.00

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article

Molecular basis of type VI secretion system effector loading

Aravindan Ilangovan, Alain Filloux, Sujatha Subramoni, Steven D. Kelly et al.
Nature Microbiology
Vibrio bacteria research studies
article

Molecular basis of type VI secretion system effector loading

Aravindan Ilangovan, Alain Filloux, Sujatha Subramoni, Steven D. Kelly, Jonasz B. Patkowski, Patricia Paracuellos, Kevin Macé, Oleksii Omelchenko, Ambre Bexter, Tiago R. D. Costa, John C. Whitney
article en

Abstract

Type VI secretion systems (T6SSs) are widespread bacterial nanomachines that deliver effectors into prokaryotic and eukaryotic cells. How an effector cargo is recruited and loaded into the Hcp ring assemblies that form the tube injected by the T6SS remains poorly understood. Pseudomonas aeruginosa has four T6SSs, each associated with a different Hcp protein. Here we use cryo-electron microscopy to resolve the structure of the Tce1 cargo loaded into a Hcp3 ring from the P. aeruginosa H3-T6SS. We show that a single Tce1 monomer interacts asymmetrically with, and is enclosed by, two hexameric Hcp3 rings, engaging key residues lining the inner surface of the Hcp3 disc. Our data indicate a stepwise loading mechanism, where an initial heterodimeric Hcp-cargo complex forms before ring encapsulation around the effector. Structural modelling suggests similar effector-Hcp3 interactions for a second T6SS effector, Tce2, which has antifungal activity. We propose that this mechanism enables coordinated delivery of a broad payload into target cells.

Nature Microbiology
Centre National de la Recherche Scientifique (FR), Queen Mary University of London (GB), Nanyang Technological University (SG), NIHR Imperial Biomedical Research Centre (GB), Institut de génétique et de développement de Rennes (FR), Singapore Centre for Environmental Life Sciences Engineering (SG), Imperial College London (GB), McMaster University (CA)
Wellcome, Ministry of Education - Singapore, Canadian Institutes of Health Research, Medical Research Council
Life below water
Openalex Percentile: Top 7%
Vibrio bacteria research studies
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