Priming mycobacterial ESX-secreted protein B to form a channel-like structure

A. Gijsbers, V. Vinciauskaite, A. Siroy, Y. Gao, G. Tria, A. Mathew, N. Sanchez-Puig, C. Lopez-Iglesias, P.J. Peters*, R.B.G. Ravelli*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

ESX-1 is a major virulence factor of Mycobacterium tuberculosis, a secretion machinery directly involved in the survival of the microorganism from the immune system defence. It disrupts the phagosome membrane of the host cell through a contact-dependent mechanism. Recently, the structure of the inner-membrane core complex of the homologous ESX-3 and ESX-5 was resolved; however, the elements involved in the secretion through the outer membrane or those acting on the host cell membrane are unknown. Protein substrates might form this missing element. Here, we describe the oligomerisation process of the ESX-1 substrate EspB, which occurs upon cleavage of its C-terminal region and is favoured by an acidic environment. Cryo-electron microscopy data shows that quaternary structure of EspB is conserved across slow growing species, but not in the fast growing M. smegmatis. EspB assembles into a channel with dimensions and characteristics suitable for the transit of ESX-1 substrates, as shown by the presence of another EspB trapped within. Our results provide insight into the structure and assembly of EspB, and suggests a possible function as a structural element of ESX-1.
Original languageEnglish
Pages (from-to)153-164
Number of pages12
JournalCurrent Research in Structural Biology
Volume3
DOIs
Publication statusPublished - 2021

Keywords

  • Cryo-EM
  • EspB
  • ESX-1
  • Mycobacteria
  • Preferential orientation
  • VII SECRETION
  • CRYO-EM
  • OUTER-MEMBRANE
  • TUBERCULOSIS
  • SYSTEM
  • VIRULENCE
  • HELIX
  • ELECTROSTATICS
  • VISUALIZATION
  • TRANSLOCATION

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