Mycobacterium tuberculosis SatS is a chaperone for the SecA2 protein export pathway
- University of North Carolina at Chapel Hill, United States
- Texas A&M University, United States
Abstract
The SecA2 protein export system is critical for the virulence of Mycobacterium tuberculosis. However, the mechanism of this export pathway remains unclear. Through a screen for suppressors of a secA2 mutant, we identified a new player in the mycobacterial SecA2 pathway that we named SatS for SecA2 (two) Suppressor. In M. tuberculosis, SatS is required for the export of a subset of SecA2 substrates and for growth in macrophages. We further identify a role for SatS as a protein export chaperone. SatS exhibits multiple properties of a chaperone, including the ability to bind to and protect substrates from aggregation. Our structural studies of SatS reveal a distinct combination of a new fold and hydrophobic grooves resembling preprotein-binding sites of the SecB chaperone. These results are significant in better defining a molecular pathway for M. tuberculosis pathogenesis and in expanding our appreciation of the diversity among chaperones and protein export systems.
Data availability
All data generated and analysed during this study are included in the manuscript and supporting files. Figure supplements have been provided for Figures 1, 2, 5, and 8. Two additional supplementary tables describe the primers and plasmids used in this study. SatS C domain X-ray structure validation details are described in Figure 8-figure supplement 1 and have been deposited in PDB under the accession codes 6DRQ and 6DNM.
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The crystal structure of SatS c-terminal domainProtein Data Bank, 6DNM.
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Crystal Structure of SecB from Escherichia coliProtein Data Bank, 1QYN.
Article and author information
Author details
Funding
National Institute of Allergy and Infectious Diseases (AI054540)
- Brittany K Miller
- Lauren S Ligon
- Nathan W Rigel
- Seidu Malik
- Miriam Braunstein
National Institute of Allergy and Infectious Diseases (A-0015)
- Ryan Hughes
- James C Sacchettini
Welch Foundation (A-0015)
- Ryan Hughes
- James C Sacchettini
University of North Carolina (Graduate School Disseration Award)
- Brittany K Miller
National Institute of General Medical Sciences (GM055336)
- Brandon R Anjuwon-Foster
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal care and experimental protocols were in strict accordance with the NIH Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee of the University of North Carolina (protocol number 15-018.0).
Copyright
© 2019, Miller 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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Mycobacterium tuberculosis SatS is a chaperone for the SecA2 protein export pathway
eLife 8:e40063.
https://doi.org/10.7554/eLife.40063
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