Cargando…

Membrane insertion of α-xenorhabdolysin in near-atomic detail

α-Xenorhabdolysins (Xax) are α-pore-forming toxins (α-PFT) that form 1–1.3 MDa large pore complexes to perforate the host cell membrane. PFTs are used by a variety of bacterial pathogens to attack host cells. Due to the lack of structural information, the molecular mechanism of action of Xax toxins...

Descripción completa

Detalles Bibliográficos
Autores principales: Schubert, Evelyn, Vetter, Ingrid R, Prumbaum, Daniel, Penczek, Pawel A, Raunser, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086661/
https://www.ncbi.nlm.nih.gov/pubmed/30010541
http://dx.doi.org/10.7554/eLife.38017
_version_ 1783346552230641664
author Schubert, Evelyn
Vetter, Ingrid R
Prumbaum, Daniel
Penczek, Pawel A
Raunser, Stefan
author_facet Schubert, Evelyn
Vetter, Ingrid R
Prumbaum, Daniel
Penczek, Pawel A
Raunser, Stefan
author_sort Schubert, Evelyn
collection PubMed
description α-Xenorhabdolysins (Xax) are α-pore-forming toxins (α-PFT) that form 1–1.3 MDa large pore complexes to perforate the host cell membrane. PFTs are used by a variety of bacterial pathogens to attack host cells. Due to the lack of structural information, the molecular mechanism of action of Xax toxins is poorly understood. Here, we report the cryo-EM structure of the XaxAB pore complex from Xenorhabdus nematophila and the crystal structures of the soluble monomers of XaxA and XaxB. The structures reveal that XaxA and XaxB are built similarly and appear as heterodimers in the 12–15 subunits containing pore, classifying XaxAB as bi-component α-PFT. Major conformational changes in XaxB, including the swinging out of an amphipathic helix are responsible for membrane insertion. XaxA acts as an activator and stabilizer for XaxB that forms the actual transmembrane pore. Based on our results, we propose a novel structural model for the mechanism of Xax intoxication.
format Online
Article
Text
id pubmed-6086661
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-60866612018-08-13 Membrane insertion of α-xenorhabdolysin in near-atomic detail Schubert, Evelyn Vetter, Ingrid R Prumbaum, Daniel Penczek, Pawel A Raunser, Stefan eLife Microbiology and Infectious Disease α-Xenorhabdolysins (Xax) are α-pore-forming toxins (α-PFT) that form 1–1.3 MDa large pore complexes to perforate the host cell membrane. PFTs are used by a variety of bacterial pathogens to attack host cells. Due to the lack of structural information, the molecular mechanism of action of Xax toxins is poorly understood. Here, we report the cryo-EM structure of the XaxAB pore complex from Xenorhabdus nematophila and the crystal structures of the soluble monomers of XaxA and XaxB. The structures reveal that XaxA and XaxB are built similarly and appear as heterodimers in the 12–15 subunits containing pore, classifying XaxAB as bi-component α-PFT. Major conformational changes in XaxB, including the swinging out of an amphipathic helix are responsible for membrane insertion. XaxA acts as an activator and stabilizer for XaxB that forms the actual transmembrane pore. Based on our results, we propose a novel structural model for the mechanism of Xax intoxication. eLife Sciences Publications, Ltd 2018-07-16 /pmc/articles/PMC6086661/ /pubmed/30010541 http://dx.doi.org/10.7554/eLife.38017 Text en © 2018, Schubert et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Microbiology and Infectious Disease
Schubert, Evelyn
Vetter, Ingrid R
Prumbaum, Daniel
Penczek, Pawel A
Raunser, Stefan
Membrane insertion of α-xenorhabdolysin in near-atomic detail
title Membrane insertion of α-xenorhabdolysin in near-atomic detail
title_full Membrane insertion of α-xenorhabdolysin in near-atomic detail
title_fullStr Membrane insertion of α-xenorhabdolysin in near-atomic detail
title_full_unstemmed Membrane insertion of α-xenorhabdolysin in near-atomic detail
title_short Membrane insertion of α-xenorhabdolysin in near-atomic detail
title_sort membrane insertion of α-xenorhabdolysin in near-atomic detail
topic Microbiology and Infectious Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086661/
https://www.ncbi.nlm.nih.gov/pubmed/30010541
http://dx.doi.org/10.7554/eLife.38017
work_keys_str_mv AT schubertevelyn membraneinsertionofaxenorhabdolysininnearatomicdetail
AT vetteringridr membraneinsertionofaxenorhabdolysininnearatomicdetail
AT prumbaumdaniel membraneinsertionofaxenorhabdolysininnearatomicdetail
AT penczekpawela membraneinsertionofaxenorhabdolysininnearatomicdetail
AT raunserstefan membraneinsertionofaxenorhabdolysininnearatomicdetail