Structural analysis of the Legionella pneumophila Dot/Icm Type IV Secretion System Core Complex
- University Of Michigan, United States
- Vanderbilt University Medical Center, United States
- University of Michigan, United States
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.
Data availability
All cryo-EM data included in this manuscript are available through the Electron Microscopy Data Bank (EMD-22068, EMD-22069, EMD-22070 and EMD-22071). All models that were constructed from these data are available via the Protein Data Bank (PDB 6x62, 6x64, 6x65, and 6x66).
Article and author information
Author details
Funding
National Institute of Allergy and Infectious Diseases (F32 AI150027-01)
- Clarissa L Durie
National Institute of General Medical Sciences (S10OD020011)
- Melanie D Ohi
National Institute of Allergy and Infectious Diseases (2T32DK007673)
- Michele Swanson
National Institute of Allergy and Infectious Diseases (R01AI118932)
- Melanie D Ohi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Andrew P Carter, MRC Laboratory of Molecular Biology, United Kingdom
Version history
- Received: June 1, 2020
- Accepted: September 1, 2020
- Accepted Manuscript published: September 2, 2020 (version 1)
- Version of Record published: September 23, 2020 (version 2)
Copyright
© 2020, Durie et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Structural analysis of the Legionella pneumophila Dot/Icm Type IV Secretion System Core Complex
eLife 9:e59530.
https://doi.org/10.7554/eLife.59530
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