Structure of a Rhs effector clade domain provides mechanistic insights into type VI secretion system toxin delivery.

Hayes, BK; Harper, M; Venugopal, H; Lewis, JM; Wright, A; Lee, H-C; Steele, JR; Steer, DL; Schittenhelm, RB; Boyce, JD; McGowan, S

Structure of a Rhs effector clade domain provides mechanistic insights into type VI secretion system toxin delivery.

Hayes, BK Harper, M Venugopal, H Lewis, JM Wright, A Lee, H-C Steele, JR Steer, DL Schittenhelm, RB Boyce, JD McGowan, S

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Publisher:: NATURE PORTFOLIO
Publication Type:: Journal Article
Citation:: Nat Commun, 2024, 15, (1), pp. 8709
Issue Date:: 2024-10-08

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Field	Value	Language
dc.contributor.author	Hayes, BK
dc.contributor.author	Harper, M
dc.contributor.author	Venugopal, H
dc.contributor.author	Lewis, JM
dc.contributor.author	Wright, A
dc.contributor.author	Lee, H-C
dc.contributor.author	Steele, JR
dc.contributor.author	Steer, DL
dc.contributor.author	Schittenhelm, RB
dc.contributor.author	Boyce, JD
dc.contributor.author	McGowan, S
dc.date.accessioned	2024-12-02T01:04:22Z
dc.date.available	2024-09-26
dc.date.available	2024-12-02T01:04:22Z
dc.date.issued	2024-10-08
dc.identifier.citation	Nat Commun, 2024, 15, (1), pp. 8709
dc.identifier.issn	2041-1723
dc.identifier.issn	2041-1723
dc.identifier.uri	http://hdl.handle.net/10453/182200
dc.description.abstract	The type VI secretion system (T6SS) is a molecular machine utilised by many Gram-negative bacteria to deliver antibacterial toxins into adjacent cells. Here we present the structure of Tse15, a T6SS Rhs effector from the nosocomial pathogen Acinetobacter baumannii. Tse15 forms a triple layered β-cocoon Rhs domain with an N-terminal α-helical clade domain and an unfolded C-terminal toxin domain inside the Rhs cage. Tse15 is cleaved into three domains, through independent auto-cleavage events involving aspartyl protease activity for toxin self-cleavage and a nucleophilic glutamic acid for N-terminal clade cleavage. Proteomic analyses identified that significantly more peptides from the N-terminal clade and toxin domains were secreted than from the Rhs cage, suggesting toxin delivery often occurs without the cage. We propose the clade domain acts as an internal chaperone to mediate toxin tethering to the T6SS machinery. Conservation of the clade domain in other Gram-negative bacteria suggests this may be a common mechanism for delivery.
dc.format	Electronic
dc.language	eng
dc.publisher	NATURE PORTFOLIO
dc.relation.ispartof	Nat Commun
dc.relation.isbasedon	10.1038/s41467-024-52950-x
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.mesh	Type VI Secretion Systems
dc.subject.mesh	Bacterial Toxins
dc.subject.mesh	Acinetobacter baumannii
dc.subject.mesh	Bacterial Proteins
dc.subject.mesh	Protein Domains
dc.subject.mesh	Models, Molecular
dc.subject.mesh	Proteomics
dc.subject.mesh	Amino Acid Sequence
dc.subject.mesh	Crystallography, X-Ray
dc.subject.mesh	Acinetobacter baumannii
dc.subject.mesh	Bacterial Proteins
dc.subject.mesh	Bacterial Toxins
dc.subject.mesh	Crystallography, X-Ray
dc.subject.mesh	Proteomics
dc.subject.mesh	Amino Acid Sequence
dc.subject.mesh	Models, Molecular
dc.subject.mesh	Type VI Secretion Systems
dc.subject.mesh	Protein Domains
dc.subject.mesh	Type VI Secretion Systems
dc.subject.mesh	Bacterial Toxins
dc.subject.mesh	Acinetobacter baumannii
dc.subject.mesh	Bacterial Proteins
dc.subject.mesh	Protein Domains
dc.subject.mesh	Models, Molecular
dc.subject.mesh	Proteomics
dc.subject.mesh	Amino Acid Sequence
dc.subject.mesh	Crystallography, X-Ray
dc.title	Structure of a Rhs effector clade domain provides mechanistic insights into type VI secretion system toxin delivery.
dc.type	Journal Article
utslib.citation.volume	15
utslib.location.activity	England
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Provost
pubs.organisational-group	University of Technology Sydney/Provost/Jumbunna
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2024-12-02T01:04:17Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	15
utslib.citation.issue	1

Abstract:

The type VI secretion system (T6SS) is a molecular machine utilised by many Gram-negative bacteria to deliver antibacterial toxins into adjacent cells. Here we present the structure of Tse15, a T6SS Rhs effector from the nosocomial pathogen Acinetobacter baumannii. Tse15 forms a triple layered β-cocoon Rhs domain with an N-terminal α-helical clade domain and an unfolded C-terminal toxin domain inside the Rhs cage. Tse15 is cleaved into three domains, through independent auto-cleavage events involving aspartyl protease activity for toxin self-cleavage and a nucleophilic glutamic acid for N-terminal clade cleavage. Proteomic analyses identified that significantly more peptides from the N-terminal clade and toxin domains were secreted than from the Rhs cage, suggesting toxin delivery often occurs without the cage. We propose the clade domain acts as an internal chaperone to mediate toxin tethering to the T6SS machinery. Conservation of the clade domain in other Gram-negative bacteria suggests this may be a common mechanism for delivery.

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http://hdl.handle.net/10453/182200