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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/59495 |
| _version_ | 1797997604749967360 |
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| author | Michael J Sheedlo Jeong Min Chung Neha Sawhney Clarissa L Durie Timothy L Cover Melanie D Ohi D Borden Lacy |
| author_facet | Michael J Sheedlo Jeong Min Chung Neha Sawhney Clarissa L Durie Timothy L Cover Melanie D Ohi D Borden Lacy |
| author_sort | Michael J Sheedlo |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T10:35:26Z |
| format | Article |
| id | doaj.art-1dde8d85688348948d757c443b00197a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T10:35:26Z |
| publishDate | 2020-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-1dde8d85688348948d757c443b00197a2022-12-22T04:29:18ZengeLife Sciences Publications LtdeLife2050-084X2020-09-01910.7554/eLife.59495Cryo-EM reveals species-specific components within the Helicobacter pylori Cag type IV secretion system core complexMichael J Sheedlo0https://orcid.org/0000-0002-3185-1727Jeong Min Chung1https://orcid.org/0000-0002-4285-8764Neha Sawhney2https://orcid.org/0000-0002-4943-1018Clarissa L Durie3https://orcid.org/0000-0002-4027-4386Timothy L Cover4https://orcid.org/0000-0001-8503-002XMelanie D Ohi5https://orcid.org/0000-0003-1750-4793D Borden Lacy6https://orcid.org/0000-0003-2273-8121Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, United StatesLife Sciences Institute, University of Michigan, Ann Arbor, United StatesDepartment of Medicine, Vanderbilt University School of Medicine, Nashville, United StatesLife Sciences Institute, University of Michigan, Ann Arbor, United StatesDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, United States; Department of Medicine, Vanderbilt University School of Medicine, Nashville, United States; Veterans Affairs Tennessee Valley Healthcare System, Nashville, United StatesLife Sciences Institute, University of Michigan, Ann Arbor, United States; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, United StatesDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, United States; Veterans Affairs Tennessee Valley Healthcare System, Nashville, United StatesThe 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.https://elifesciences.org/articles/59495Helicobacter pyloritype iv secretionmolecular machinecryo-electron microscopygastric cancerbacterial protein secretion |
| spellingShingle | Michael J Sheedlo Jeong Min Chung Neha Sawhney Clarissa L Durie Timothy L Cover Melanie D Ohi D Borden Lacy Cryo-EM reveals species-specific components within the Helicobacter pylori Cag type IV secretion system core complex eLife Helicobacter pylori type iv secretion molecular machine cryo-electron microscopy gastric cancer bacterial protein secretion |
| 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 | Helicobacter pylori type iv secretion molecular machine cryo-electron microscopy gastric cancer bacterial protein secretion |
| url | https://elifesciences.org/articles/59495 |
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