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bioRxiv · 10.1101/2025.01.24.634720

A ubiquitin-like protein controls assembly of a bacterial Type VIIb secretion system

Oka, G. U.·Benoit, N.·Siroy, A.·Gubellini, F.·Marza, E.·Fronzes, R.
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Abstract

Type VII secretion systems (T7SS) are crucial bacterial nanomachines that mediate interbacterial competition and host-pathogen interactions in Gram-positive bacteria. Despite their importance, the structural basis for assembly and substrate transport in T7SSb, a widely distributed T7SS variant, remains poorly understood. Here, we present the cryo-EM structure of the T7SSb core complex from Bacillus subtilis, revealing how a ubiquitin-like protein, YukD, coordinates assembly of the secretion machinery. YukD forms extensive interactions with the central channel component YukB and promotes its association with the pseudokinase YukC, creating a stable building block for channel assembly. Using microscopy and competition assays, we demonstrate that YukD is essential for proper T7SSb complex formation and contact-dependent bacterial killing. Structural modeling suggests this YukD-dependent assembly mechanism is conserved across diverse Gram-positive bacteria. Our findings reveal how bacteria have adapted a ubiquitin-like protein as a structural regulator for assembling a large secretion complex.

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Oka, G. U., Benoit, N., Siroy, A., Gubellini, F., Marza, E., Fronzes, R.. 2025-01-24. A ubiquitin-like protein controls assembly of a bacterial Type VIIb secretion system. https://doi.org/10.1101/2025.01.24.634720

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