Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Structure and dynamics of the ESX-5 type VII secretion system of Mycobacterium tuberculosis

Catalin M. Bunduc, Dirk Fahrenkamp, Jiri Wald, Roy Ummels, Wilbert Bitter, Edith N.G. Houben, Thomas C. Marlovits
doi: https://doi.org/10.1101/2020.12.02.408906
Catalin M. Bunduc
1Centre for Structural Systems Biology, Notkestraße 85, 22607 Hamburg, Germany
2Institute of Structural and Systems Biology, University Medical Center Hamburg-Eppendorf, Notkestraße 85, 22607 Hamburg, Germany
3German Electron Synchrotron Centre Notkestraße 85, 22607 Hamburg, Germany
4Section Molecular Microbiology, Amsterdam Institute of Molecular and Life Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dirk Fahrenkamp
1Centre for Structural Systems Biology, Notkestraße 85, 22607 Hamburg, Germany
2Institute of Structural and Systems Biology, University Medical Center Hamburg-Eppendorf, Notkestraße 85, 22607 Hamburg, Germany
3German Electron Synchrotron Centre Notkestraße 85, 22607 Hamburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jiri Wald
1Centre for Structural Systems Biology, Notkestraße 85, 22607 Hamburg, Germany
2Institute of Structural and Systems Biology, University Medical Center Hamburg-Eppendorf, Notkestraße 85, 22607 Hamburg, Germany
3German Electron Synchrotron Centre Notkestraße 85, 22607 Hamburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roy Ummels
5Department of Medical Microbiology and Infection Control, Amsterdam Infection & Immunity Institute, Amsterdam UMC, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wilbert Bitter
4Section Molecular Microbiology, Amsterdam Institute of Molecular and Life Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands
5Department of Medical Microbiology and Infection Control, Amsterdam Infection & Immunity Institute, Amsterdam UMC, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Edith N.G. Houben
4Section Molecular Microbiology, Amsterdam Institute of Molecular and Life Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas C. Marlovits
1Centre for Structural Systems Biology, Notkestraße 85, 22607 Hamburg, Germany
2Institute of Structural and Systems Biology, University Medical Center Hamburg-Eppendorf, Notkestraße 85, 22607 Hamburg, Germany
3German Electron Synchrotron Centre Notkestraße 85, 22607 Hamburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: marlovits@marlovitslab.org
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Mycobacterium tuberculosis causes one of the most important infectious diseases in humans, leading to 1.5 million deaths every year. Specialized protein transport systems, called type VII secretion systems (T7SSs), are central for its virulence, but also crucial for nutrient and metabolite transport across the mycobacterial cell envelope. Here we present the first structure of an intact T7SS inner membrane complex of M. tuberculosis. We show how the 2.32 MDa, 165 transmembrane helices-containing ESX-5 assembly is restructured and stabilized as a trimer of dimers by the MycP5 protease. A trimer of MycP5 caps a central periplasmic dome-like chamber formed by three EccB5 dimers, with the proteolytic sites facing towards the cavity. This chamber suggests a central secretion and processing conduit. Complexes without MycP5 show disruption of the EccB5 periplasmic assembly and increased flexibility, highlighting the importance of this component for complex integrity. Beneath the EccB5-MycP5 chamber, dimers of the EccC5 ATPase assemble into three four-transmembrane helix bundles, which together seal the potential central secretion channel. Individual cytoplasmic EccC5 domains adopt two distinctive conformations, likely reflecting different secretion states. Our work suggests a novel mechanism of protein transport and provides a structural scaffold to aid drug development against the major human pathogen.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted December 02, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Structure and dynamics of the ESX-5 type VII secretion system of Mycobacterium tuberculosis
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Structure and dynamics of the ESX-5 type VII secretion system of Mycobacterium tuberculosis
Catalin M. Bunduc, Dirk Fahrenkamp, Jiri Wald, Roy Ummels, Wilbert Bitter, Edith N.G. Houben, Thomas C. Marlovits
bioRxiv 2020.12.02.408906; doi: https://doi.org/10.1101/2020.12.02.408906
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Structure and dynamics of the ESX-5 type VII secretion system of Mycobacterium tuberculosis
Catalin M. Bunduc, Dirk Fahrenkamp, Jiri Wald, Roy Ummels, Wilbert Bitter, Edith N.G. Houben, Thomas C. Marlovits
bioRxiv 2020.12.02.408906; doi: https://doi.org/10.1101/2020.12.02.408906

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Microbiology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3592)
  • Biochemistry (7562)
  • Bioengineering (5508)
  • Bioinformatics (20762)
  • Biophysics (10309)
  • Cancer Biology (7967)
  • Cell Biology (11627)
  • Clinical Trials (138)
  • Developmental Biology (6602)
  • Ecology (10190)
  • Epidemiology (2065)
  • Evolutionary Biology (13594)
  • Genetics (9532)
  • Genomics (12834)
  • Immunology (7917)
  • Microbiology (19525)
  • Molecular Biology (7651)
  • Neuroscience (42027)
  • Paleontology (307)
  • Pathology (1254)
  • Pharmacology and Toxicology (2196)
  • Physiology (3263)
  • Plant Biology (7029)
  • Scientific Communication and Education (1294)
  • Synthetic Biology (1949)
  • Systems Biology (5422)
  • Zoology (1114)