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Cryo-EM reveals species-specific components within the Helicobacter pylori Cag type IV secretion system core complex
The pathogenesis of Helicobacter pylori-associated gastric cancer is dependent on delivery of CagA into host cells through a type IV secretion system (T4SS). The H. pylori Cag T4SS includes a large membrane-spanning core complex containing five proteins, organized into an outer membrane cap (OMC), a...
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/PMC7511236/ https://www.ncbi.nlm.nih.gov/pubmed/32876048 http://dx.doi.org/10.7554/eLife.59495 |
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author | Sheedlo, Michael J Chung, Jeong Min Sawhney, Neha Durie, Clarissa L Cover, Timothy L Ohi, Melanie D Lacy, D Borden |
author_facet | Sheedlo, Michael J Chung, Jeong Min Sawhney, Neha Durie, Clarissa L Cover, Timothy L Ohi, Melanie D Lacy, D Borden |
author_sort | Sheedlo, Michael J |
collection | PubMed |
description | The pathogenesis of Helicobacter pylori-associated gastric cancer is dependent on delivery of CagA into host cells through a type IV secretion system (T4SS). The H. pylori Cag T4SS includes a large membrane-spanning core complex containing five proteins, organized into an outer membrane cap (OMC), a periplasmic ring (PR) and a stalk. Here, we report cryo-EM reconstructions of a core complex lacking Cag3 and an improved map of the wild-type complex. We define the structures of two unique species-specific components (Cag3 and CagM) and show that Cag3 is structurally similar to CagT. Unexpectedly, components of the OMC are organized in a 1:1:2:2:5 molar ratio (CagY:CagX:CagT:CagM:Cag3). CagX and CagY are components of both the OMC and the PR and bridge the symmetry mismatch between these regions. These results reveal that assembly of the H. pylori T4SS core complex is dependent on incorporation of interwoven species-specific components. |
format | Online Article Text |
id | pubmed-7511236 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-75112362020-09-25 Cryo-EM reveals species-specific components within the Helicobacter pylori Cag type IV secretion system core complex Sheedlo, Michael J Chung, Jeong Min Sawhney, Neha Durie, Clarissa L Cover, Timothy L Ohi, Melanie D Lacy, D Borden eLife Microbiology and Infectious Disease The pathogenesis of Helicobacter pylori-associated gastric cancer is dependent on delivery of CagA into host cells through a type IV secretion system (T4SS). The H. pylori Cag T4SS includes a large membrane-spanning core complex containing five proteins, organized into an outer membrane cap (OMC), a periplasmic ring (PR) and a stalk. Here, we report cryo-EM reconstructions of a core complex lacking Cag3 and an improved map of the wild-type complex. We define the structures of two unique species-specific components (Cag3 and CagM) and show that Cag3 is structurally similar to CagT. Unexpectedly, components of the OMC are organized in a 1:1:2:2:5 molar ratio (CagY:CagX:CagT:CagM:Cag3). CagX and CagY are components of both the OMC and the PR and bridge the symmetry mismatch between these regions. These results reveal that assembly of the H. pylori T4SS core complex is dependent on incorporation of interwoven species-specific components. eLife Sciences Publications, Ltd 2020-09-02 /pmc/articles/PMC7511236/ /pubmed/32876048 http://dx.doi.org/10.7554/eLife.59495 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 | Microbiology and Infectious Disease Sheedlo, Michael J Chung, Jeong Min Sawhney, Neha Durie, Clarissa L Cover, Timothy L Ohi, Melanie D Lacy, D Borden Cryo-EM reveals species-specific components within the Helicobacter pylori Cag type IV secretion system core complex |
title | Cryo-EM reveals species-specific components within the Helicobacter pylori Cag type IV secretion system core complex |
title_full | Cryo-EM reveals species-specific components within the Helicobacter pylori Cag type IV secretion system core complex |
title_fullStr | Cryo-EM reveals species-specific components within the Helicobacter pylori Cag type IV secretion system core complex |
title_full_unstemmed | Cryo-EM reveals species-specific components within the Helicobacter pylori Cag type IV secretion system core complex |
title_short | Cryo-EM reveals species-specific components within the Helicobacter pylori Cag type IV secretion system core complex |
title_sort | cryo-em reveals species-specific components within the helicobacter pylori cag type iv secretion system core complex |
topic | Microbiology and Infectious Disease |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511236/ https://www.ncbi.nlm.nih.gov/pubmed/32876048 http://dx.doi.org/10.7554/eLife.59495 |
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