Characterisation of a tripartite α-pore forming toxin from Serratia marcescens

Abstract

Tripartite members of the ClyA family of α-PFTs have recently been identified in a number of pathogenic Gram-negative bacteria, including the human pathogen Serratia marcescens. Structures of a Gram-negative A component and a tripartite α-PFT complete pore are unknown and a mechanism for pore formation is still uncertain. Here we characterise the tripartite SmhABC toxin from S. marcescens and propose a mechanism of pore assembly. We present the structure of soluble SmhA, as well as the soluble and pore forms of SmhB. We show that the β-tongue soluble structure is well conserved in the family and propose two conserved latches between the head and tail domains that are broken on the soluble to pore conformational change. Using the structures of individual components, sequence analysis and docking predictions we illustrate how the A, B and C protomers would assemble on the membrane to produce a complete tripartite α-PFT pore.

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Item Type:	Article
Authors/Creators:	Churchill-Angus, A.M. Schofield, T.H.B. Marlow, T.R. Sedelnikova, S.E. https://orcid.org/0000-0001-5174-6302 Wilson, J.S. https://orcid.org/0000-0002-6967-0809 Rafferty, J.B. https://orcid.org/0000-0003-1183-7474 Baker, P.J. https://orcid.org/0000-0003-1995-5643
Copyright, Publisher and Additional Information:	© 2021 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Dates:	Published: 19 March 2021 Published (online): 19 March 2021 Accepted: 3 March 2021
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield)
Funding Information:	Funder Grant number Engineering and Physical Science Research Council EP/L026872/1 Biotechnology and Biological Sciences Research Council BB/F016832/1
Depositing User:	Symplectic Sheffield
Date Deposited:	08 Apr 2021 07:42
Last Modified:	08 Apr 2021 07:42
Status:	Published
Publisher:	Springer Nature
Refereed:	Yes
Identification Number:	10.1038/s41598-021-85726-0
Related URLs:	PubMed URL
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:172798

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Characterisation of a tripartite α-pore forming toxin from Serratia marcescens

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