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Structural analysis of the Legionella pneumophila Dot/Icm Type IV Secretion System Core Complex

View ORCID ProfileClarissa L. Durie, View ORCID ProfileMichael J. Sheedlo, View ORCID ProfileJeong Min Chung, Brenda G. Byrne, Min Su, Thomas Knight, View ORCID ProfileMichele S. Swanson, View ORCID ProfileD. Borden Lacy, View ORCID ProfileMelanie D. Ohi
doi: https://doi.org/10.1101/2020.08.28.271460
Clarissa L. Durie
1Life Sciences Institute, University of Michigan, Ann Arbor MI, USA
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Michael J. Sheedlo
2Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville TN, USA
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  • ORCID record for Michael J. Sheedlo
Jeong Min Chung
1Life Sciences Institute, University of Michigan, Ann Arbor MI, USA
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Brenda G. Byrne
3Department of Microbiology and Immunology, University of Michigan, Ann Arbor MI, USA
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Min Su
1Life Sciences Institute, University of Michigan, Ann Arbor MI, USA
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Thomas Knight
3Department of Microbiology and Immunology, University of Michigan, Ann Arbor MI, USA
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Michele S. Swanson
3Department of Microbiology and Immunology, University of Michigan, Ann Arbor MI, USA
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  • For correspondence: mohi@umich.edu
D. Borden Lacy
2Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville TN, USA
4The Veterans Affairs Tennessee Valley Healthcare System, Nashville TN, USA
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  • For correspondence: mohi@umich.edu
Melanie D. Ohi
1Life Sciences Institute, University of Michigan, Ann Arbor MI, USA
5Department of Cell and Developmental Biology, University of Michigan, Ann Arbor MI, USA
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  • For correspondence: mohi@umich.edu
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Abstract

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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Posted August 28, 2020.
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Structural analysis of the Legionella pneumophila Dot/Icm Type IV Secretion System Core Complex
Clarissa L. Durie, Michael J. Sheedlo, Jeong Min Chung, Brenda G. Byrne, Min Su, Thomas Knight, Michele S. Swanson, D. Borden Lacy, Melanie D. Ohi
bioRxiv 2020.08.28.271460; doi: https://doi.org/10.1101/2020.08.28.271460
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Structural analysis of the Legionella pneumophila Dot/Icm Type IV Secretion System Core Complex
Clarissa L. Durie, Michael J. Sheedlo, Jeong Min Chung, Brenda G. Byrne, Min Su, Thomas Knight, Michele S. Swanson, D. Borden Lacy, Melanie D. Ohi
bioRxiv 2020.08.28.271460; doi: https://doi.org/10.1101/2020.08.28.271460

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