Complete structures of the YenTc holotoxin prepore and pore reveal the evolutionary basis for chitinase incorporation into ABC toxins.

Low, YS; Roche, SG; Aleksandrova, NA; Foley, G; Low, JK; Box, JK; Croll, TI; Chassagnon, IR; Lott, JS; Deplazes, E; Bodén, M; Hurst, MR; Piper, SJ; Landsberg, MJ

Complete structures of the YenTc holotoxin prepore and pore reveal the evolutionary basis for chitinase incorporation into ABC toxins.

Low, YS Roche, SG Aleksandrova, NA Foley, G Low, JK Box, JK Croll, TI Chassagnon, IR Lott, JS Deplazes, E

Bodén, M Hurst, MR Piper, SJ Landsberg, MJ

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Publisher:: NATURE PORTFOLIO
Publication Type:: Journal Article
Citation:: Nat Commun, 2025, 16, (1), pp. 11121
Issue Date:: 2025-12-15

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Field	Value	Language
dc.contributor.author	Low, YS
dc.contributor.author	Roche, SG
dc.contributor.author	Aleksandrova, NA
dc.contributor.author	Foley, G
dc.contributor.author	Low, JK
dc.contributor.author	Box, JK
dc.contributor.author	Croll, TI
dc.contributor.author	Chassagnon, IR
dc.contributor.author	Lott, JS
dc.contributor.author	Deplazes, E https://orcid.org/0000-0003-2052-5536
dc.contributor.author	Bodén, M
dc.contributor.author	Hurst, MR
dc.contributor.author	Piper, SJ
dc.contributor.author	Landsberg, MJ
dc.date.accessioned	2026-02-03T09:11:46Z
dc.date.available	2025-10-27
dc.date.available	2026-02-03T09:11:46Z
dc.date.issued	2025-12-15
dc.identifier.citation	Nat Commun, 2025, 16, (1), pp. 11121
dc.identifier.issn	2041-1723
dc.identifier.issn	2041-1723
dc.identifier.uri	http://hdl.handle.net/10453/192882
dc.description.abstract	ABC toxins are toxin-translocating, pore-forming proteins found in a wide range of insecticidal bacteria and some mammalian pathogens. The Yersinia entomopahaga toxin complex (YenTc) belongs to a distinct subclass of ABC toxins, defined by a divergent molecular architecture. Structural details that define their mechanism of action remain to be elucidated. Here we determine structures of the YenTc holotoxin assembly in both prepore and pore-forming configurations using cryo-EM in conjunction with Alphafold2-assisted structural modelling of flexible domains. We define the structural mechanism via which enzymatically-active chitinase subunits are incorporated, and show using phylogenetic analyses that this subclass-defining feature has evolved relatively recently. Our structures point to the existence of distinct conformational states in YenTc, which may distinguish it from other structurally-characterised ABC toxins, or represent states on a shared mechanistic trajectory. Thus, our findings enhance our understanding of the structural diversity that defines distinct ABC toxin subclasses.
dc.format	Electronic
dc.language	eng
dc.publisher	NATURE PORTFOLIO
dc.relation.ispartof	Nat Commun
dc.relation.isbasedon	10.1038/s41467-025-66050-x
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.mesh	Cryoelectron Microscopy
dc.subject.mesh	Chitinases
dc.subject.mesh	Bacterial Toxins
dc.subject.mesh	Phylogeny
dc.subject.mesh	Models, Molecular
dc.subject.mesh	Yersinia
dc.subject.mesh	Evolution, Molecular
dc.subject.mesh	Bacterial Proteins
dc.subject.mesh	Protein Conformation
dc.subject.mesh	Pore Forming Cytotoxic Proteins
dc.subject.mesh	Yersinia
dc.subject.mesh	Bacterial Proteins
dc.subject.mesh	Bacterial Toxins
dc.subject.mesh	Cryoelectron Microscopy
dc.subject.mesh	Evolution, Molecular
dc.subject.mesh	Phylogeny
dc.subject.mesh	Protein Conformation
dc.subject.mesh	Models, Molecular
dc.subject.mesh	Pore Forming Cytotoxic Proteins
dc.subject.mesh	Chitinases
dc.subject.mesh	Cryoelectron Microscopy
dc.subject.mesh	Chitinases
dc.subject.mesh	Bacterial Toxins
dc.subject.mesh	Phylogeny
dc.subject.mesh	Models, Molecular
dc.subject.mesh	Yersinia
dc.subject.mesh	Evolution, Molecular
dc.subject.mesh	Bacterial Proteins
dc.subject.mesh	Protein Conformation
dc.subject.mesh	Pore Forming Cytotoxic Proteins
dc.title	Complete structures of the YenTc holotoxin prepore and pore reveal the evolutionary basis for chitinase incorporation into ABC toxins.
dc.type	Journal Article
utslib.citation.volume	16
utslib.location.activity	England
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	University of Technology Sydney/UTS Groups
pubs.organisational-group	University of Technology Sydney/UTS Groups/Chancellor's Research Fellows
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.date.updated	2026-02-03T09:11:43Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	16
utslib.citation.issue	1

Abstract:

ABC toxins are toxin-translocating, pore-forming proteins found in a wide range of insecticidal bacteria and some mammalian pathogens. The Yersinia entomopahaga toxin complex (YenTc) belongs to a distinct subclass of ABC toxins, defined by a divergent molecular architecture. Structural details that define their mechanism of action remain to be elucidated. Here we determine structures of the YenTc holotoxin assembly in both prepore and pore-forming configurations using cryo-EM in conjunction with Alphafold2-assisted structural modelling of flexible domains. We define the structural mechanism via which enzymatically-active chitinase subunits are incorporated, and show using phylogenetic analyses that this subclass-defining feature has evolved relatively recently. Our structures point to the existence of distinct conformational states in YenTc, which may distinguish it from other structurally-characterised ABC toxins, or represent states on a shared mechanistic trajectory. Thus, our findings enhance our understanding of the structural diversity that defines distinct ABC toxin subclasses.

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http://hdl.handle.net/10453/192882