Structural basis for independent pore function of Vpb4 from Bacillus thuringiensis

Wirawan, Raymond, Jamieson, W. David ORCID: https://orcid.org/0000-0001-8260-5211, Baird, Hannah M., Berry, Colin ORCID: https://orcid.org/0000-0002-9943-548X, Lupton, Christopher J., Venugopal, Hari, Valentin-Alvarado, Luis E., Best, Hannah L., Jones, D. Dafydd ORCID: https://orcid.org/0000-0001-7709-3995, Williamson, Lainey J., Auhim, Husam Sabah, Castell, Oliver K. ORCID: https://orcid.org/0000-0002-6059-8062, Dunstone, Michelle A. and Spicer, Bradley A. 2026. Structural basis for independent pore function of Vpb4 from Bacillus thuringiensis. Nature Communications 17 , 8198. 10.1038/s41467-026-74567-y

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Abstract

The Bacterial_Exotoxin_B family constitutes translocating pore-forming proteins that function as the binding (B) component in the binary AB Toxin mechanism. While the two-component system of the family is consistent among well-characterised members, the single-component Vpb4 subclass from entomopathogenic Bacillus thuringiensis challenges this dogma. Here, through single-particle cryo-electron microscopy, we elucidate the inserted pore structure of a Vpb4 member, Vpb4Aa2, at 2.2 Å resolution. The structure reveals distinguishing features from other family members: missing molecular bottleneck and neutrally charged β-barrel. Accordingly, preliminary electrophysiology studies show greater ion flux by Vpb4Aa2 compared to archetypal family member, PA. Through our findings, structure-guided database search allows identification of putative Vpb4-like proteins, which suggest a broader class of single-component proteins within the larger family. This provides mechanistic understanding of the differences between independent pores and translocating pores, with implications in the agricultural industry for screening and identification of future pest control candidates.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Pharmacy Schools > Biosciences
Publisher:	Nature Research
ISSN:	2041-1723
Funders:	BBSRC, EPSRC
Projects:	BB/Y008537/1, BB/Y008537/1, BB/T019948/1, BB/S002774/1, Physics of Life Hub 2592665
Date of First Compliant Deposit:	9 July 2026
Date of Acceptance:	2 June 2026
Last Modified:	28 Sep 2026 14:09
URI:	https://orca.cardiff.ac.uk/id/eprint/188118

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