Molecular basis for the folding of β-helical autotransporter passenger domains

Abstract

Bacterial autotransporters comprise a C-terminal β-barrel domain, which must be correctly folded and inserted into the outer membrane to facilitate translocation of the N-terminal passenger domain to the cell exterior. Once at the surface, the passenger domains of most autotransporters are folded into an elongated β-helix. In a cellular context, key molecules catalyze the assembly of the autotransporter β-barrel domain. However, how the passenger domain folds into its functional form is poorly understood. Here we use mutational analysis on the autotransporter Pet to show that the β-hairpin structure of the fifth extracellular loop of the β-barrel domain has a crucial role for passenger domain folding into a β-helix. Bioinformatics and structural analyses, and mutagenesis of a homologous autotransporter, suggest that this function is conserved among autotransporter proteins with β-helical passenger domains. We propose that the autotransporter β-barrel domain is a folding vector that nucleates folding of the passenger domain.

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Item Type:	Article
Authors/Creators:	Yuan, X Johnson, MD Zhang, J Lo, AW Schembri, MA Wijeyewickrema, LC Pike, RN Huysmans, GHM Henderson, IR Leyton, DL
Copyright, Publisher and Additional Information:	(c) 2018, 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit https://creativecommons.org/licenses/by/4.0/.
Dates:	Published: 11 April 2018 Published (online): 11 April 2018 Accepted: 27 February 2018
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds)
Depositing User:	Symplectic Publications
Date Deposited:	18 Apr 2018 15:57
Last Modified:	18 Apr 2018 15:57
Status:	Published
Publisher:	Springer Nature
Identification Number:	10.1038/s41467-018-03593-2
Related URLs:	Author
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:129753

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Molecular basis for the folding of β-helical autotransporter passenger domains

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