Structural analysis of the Legionella pneumophila Dot/Icm type IV secretion system core complex

Legionella pneumophila is an opportunistic pathogen that causes the potentially fatal pneumonia Legionnaires’ Disease. This infection and subsequent pathology require the Dot/Icm Type IV Secretion System (T4SS) to deliver effector proteins into host cells. Compared to prototypical T4SSs, the Dot/Icm...

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Main Authors: Clarissa L Durie, Michael J Sheedlo, Jeong Min Chung, Brenda G Byrne, Min Su, Thomas Knight, Michele Swanson, D Borden Lacy, Melanie D Ohi
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2020-09-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/59530
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author Clarissa L Durie
Michael J Sheedlo
Jeong Min Chung
Brenda G Byrne
Min Su
Thomas Knight
Michele Swanson
D Borden Lacy
Melanie D Ohi
author_facet Clarissa L Durie
Michael J Sheedlo
Jeong Min Chung
Brenda G Byrne
Min Su
Thomas Knight
Michele Swanson
D Borden Lacy
Melanie D Ohi
author_sort Clarissa L Durie
collection DOAJ
description Legionella pneumophila is an opportunistic pathogen that causes the potentially fatal pneumonia Legionnaires’ Disease. This infection and subsequent pathology require the Dot/Icm Type IV Secretion System (T4SS) to deliver effector proteins into host cells. Compared to prototypical T4SSs, the Dot/Icm assembly is much larger, containing ~27 different components including a core complex reported to be composed of five proteins: DotC, DotD, DotF, DotG, and DotH. Using single particle cryo-electron microscopy (cryo-EM), we report reconstructions of the core complex of the Dot/Icm T4SS that includes a symmetry mismatch between distinct structural features of the outer membrane cap (OMC) and periplasmic ring (PR). We present models of known core complex proteins, DotC, DotD, and DotH, and two structurally similar proteins within the core complex, DotK and Lpg0657. This analysis reveals the stoichiometry and contact interfaces between the key proteins of the Dot/Icm T4SS core complex and provides a framework for understanding a complex molecular machine.
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spelling doaj.art-4e727e751c3643ba8cf52314be90d2c12022-12-22T02:04:59ZengeLife Sciences Publications LtdeLife2050-084X2020-09-01910.7554/eLife.59530Structural analysis of the Legionella pneumophila Dot/Icm type IV secretion system core complexClarissa L Durie0https://orcid.org/0000-0002-4027-4386Michael J Sheedlo1https://orcid.org/0000-0002-3185-1727Jeong Min Chung2https://orcid.org/0000-0002-4285-8764Brenda G Byrne3Min Su4Thomas Knight5Michele Swanson6https://orcid.org/0000-0003-2542-0266D Borden Lacy7https://orcid.org/0000-0003-2273-8121Melanie D Ohi8https://orcid.org/0000-0003-1750-4793Life Sciences Institute, University of Michigan, Ann Arbor, United StatesDepartment of Pathology, Microbiology, and Immunology, Department of Pathology, Vanderbilt University Medical Center, Nashville, United StatesLife Sciences Institute, University of Michigan, Ann Arbor, United StatesDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, United StatesLife Sciences Institute, University of Michigan, Ann Arbor, United StatesDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, United StatesDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, United StatesDepartment of Pathology, Microbiology, and Immunology, Department of Pathology, Vanderbilt University Medical Center, Nashville, United States; The Veterans Affairs Tennessee Valley Healthcare System, Nashville, United States; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, United StatesLife Sciences Institute, University of Michigan, Ann Arbor, United StatesLegionella pneumophila is an opportunistic pathogen that causes the potentially fatal pneumonia Legionnaires’ Disease. This infection and subsequent pathology require the Dot/Icm Type IV Secretion System (T4SS) to deliver effector proteins into host cells. Compared to prototypical T4SSs, the Dot/Icm assembly is much larger, containing ~27 different components including a core complex reported to be composed of five proteins: DotC, DotD, DotF, DotG, and DotH. Using single particle cryo-electron microscopy (cryo-EM), we report reconstructions of the core complex of the Dot/Icm T4SS that includes a symmetry mismatch between distinct structural features of the outer membrane cap (OMC) and periplasmic ring (PR). We present models of known core complex proteins, DotC, DotD, and DotH, and two structurally similar proteins within the core complex, DotK and Lpg0657. This analysis reveals the stoichiometry and contact interfaces between the key proteins of the Dot/Icm T4SS core complex and provides a framework for understanding a complex molecular machine.https://elifesciences.org/articles/59530Legionella pneumophilaType IV Secretion Systemcryo-EMpathogenesis
spellingShingle Clarissa L Durie
Michael J Sheedlo
Jeong Min Chung
Brenda G Byrne
Min Su
Thomas Knight
Michele Swanson
D Borden Lacy
Melanie D Ohi
Structural analysis of the Legionella pneumophila Dot/Icm type IV secretion system core complex
eLife
Legionella pneumophila
Type IV Secretion System
cryo-EM
pathogenesis
title Structural analysis of the Legionella pneumophila Dot/Icm type IV secretion system core complex
title_full Structural analysis of the Legionella pneumophila Dot/Icm type IV secretion system core complex
title_fullStr Structural analysis of the Legionella pneumophila Dot/Icm type IV secretion system core complex
title_full_unstemmed Structural analysis of the Legionella pneumophila Dot/Icm type IV secretion system core complex
title_short Structural analysis of the Legionella pneumophila Dot/Icm type IV secretion system core complex
title_sort structural analysis of the legionella pneumophila dot icm type iv secretion system core complex
topic Legionella pneumophila
Type IV Secretion System
cryo-EM
pathogenesis
url https://elifesciences.org/articles/59530
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