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Structural insight into toxin secretion by contact-dependent growth inhibition transporters
Bacterial contact-dependent growth inhibition (CDI) systems use a type Vb secretion mechanism to export large CdiA toxins across the outer membrane by dedicated outer membrane transporters called CdiB. Here, we report the first crystal structures of two CdiB transporters from Acinetobacter baumannii...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644211/ https://www.ncbi.nlm.nih.gov/pubmed/33089781 http://dx.doi.org/10.7554/eLife.58100 |
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author | Guerin, Jeremy Botos, Istvan Zhang, Zijian Lundquist, Karl Gumbart, James C Buchanan, Susan K |
author_facet | Guerin, Jeremy Botos, Istvan Zhang, Zijian Lundquist, Karl Gumbart, James C Buchanan, Susan K |
author_sort | Guerin, Jeremy |
collection | PubMed |
description | Bacterial contact-dependent growth inhibition (CDI) systems use a type Vb secretion mechanism to export large CdiA toxins across the outer membrane by dedicated outer membrane transporters called CdiB. Here, we report the first crystal structures of two CdiB transporters from Acinetobacter baumannii and Escherichia coli. CdiB transporters adopt a TpsB fold, containing a 16-stranded transmembrane β-barrel connected to two periplasmic domains. The lumen of the CdiB pore is occluded by an N-terminal α-helix and the conserved extracellular loop 6; these two elements adopt different conformations in the structures. We identified a conserved DxxG motif located on strand β1 that connects loop 6 through different networks of interactions. Structural modifications of DxxG induce rearrangement of extracellular loops and alter interactions with the N-terminal α-helix, preparing the system for α-helix ejection. Using structural biology, functional assays, and molecular dynamics simulations, we show how the barrel pore is primed for CdiA toxin secretion. |
format | Online Article Text |
id | pubmed-7644211 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-76442112020-11-09 Structural insight into toxin secretion by contact-dependent growth inhibition transporters Guerin, Jeremy Botos, Istvan Zhang, Zijian Lundquist, Karl Gumbart, James C Buchanan, Susan K eLife Biochemistry and Chemical Biology Bacterial contact-dependent growth inhibition (CDI) systems use a type Vb secretion mechanism to export large CdiA toxins across the outer membrane by dedicated outer membrane transporters called CdiB. Here, we report the first crystal structures of two CdiB transporters from Acinetobacter baumannii and Escherichia coli. CdiB transporters adopt a TpsB fold, containing a 16-stranded transmembrane β-barrel connected to two periplasmic domains. The lumen of the CdiB pore is occluded by an N-terminal α-helix and the conserved extracellular loop 6; these two elements adopt different conformations in the structures. We identified a conserved DxxG motif located on strand β1 that connects loop 6 through different networks of interactions. Structural modifications of DxxG induce rearrangement of extracellular loops and alter interactions with the N-terminal α-helix, preparing the system for α-helix ejection. Using structural biology, functional assays, and molecular dynamics simulations, we show how the barrel pore is primed for CdiA toxin secretion. eLife Sciences Publications, Ltd 2020-10-22 /pmc/articles/PMC7644211/ /pubmed/33089781 http://dx.doi.org/10.7554/eLife.58100 Text en http://creativecommons.org/publicdomain/zero/1.0/ http://creativecommons.org/publicdomain/zero/1.0/This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (http://creativecommons.org/publicdomain/zero/1.0/) . |
spellingShingle | Biochemistry and Chemical Biology Guerin, Jeremy Botos, Istvan Zhang, Zijian Lundquist, Karl Gumbart, James C Buchanan, Susan K Structural insight into toxin secretion by contact-dependent growth inhibition transporters |
title | Structural insight into toxin secretion by contact-dependent growth inhibition transporters |
title_full | Structural insight into toxin secretion by contact-dependent growth inhibition transporters |
title_fullStr | Structural insight into toxin secretion by contact-dependent growth inhibition transporters |
title_full_unstemmed | Structural insight into toxin secretion by contact-dependent growth inhibition transporters |
title_short | Structural insight into toxin secretion by contact-dependent growth inhibition transporters |
title_sort | structural insight into toxin secretion by contact-dependent growth inhibition transporters |
topic | Biochemistry and Chemical Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644211/ https://www.ncbi.nlm.nih.gov/pubmed/33089781 http://dx.doi.org/10.7554/eLife.58100 |
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