Structural Variability of EspG Chaperones from Mycobacterial ESX-1, ESX-3, and ESX-5 Type VII Secretion Systems

Anne T. Tuukkanen, Diana Freire, Sum Chan, Mark A. Arbing, Robert W. Reed, Timothy J. Evans, Grasilda Zenkeviciutė, Jennifer Kim, Sara Kahng, Michael R. Sawaya, Catherine T. Chaton, Matthias Wilmanns, David Eisenberg, Annabel H.A. Parret, Konstantin V. Korotkov

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Type VII secretion systems (ESX) are responsible for transport of multiple proteins in mycobacteria. How different ESX systems achieve specific secretion of cognate substrates remains elusive. In the ESX systems, the cytoplasmic chaperone EspG forms complexes with heterodimeric PE–PPE substrates that are secreted from the cells or remain associated with the cell surface. Here we report the crystal structure of the EspG1 chaperone from the ESX-1 system determined using a fusion strategy with T4 lysozyme. EspG1 adopts a quasi 2-fold symmetric structure that consists of a central β-sheet and two α-helical bundles. In addition, we describe the structures of EspG3 chaperones from four different crystal forms. Alternate conformations of the putative PE–PPE binding site are revealed by comparison of the available EspG3 structures. Analysis of EspG1, EspG3, and EspG5 chaperones using small-angle X-ray scattering reveals that EspG1 and EspG3 chaperones form dimers in solution, which we observed in several of our crystal forms. Finally, we propose a model of the ESX-3 specific EspG3–PE5–PPE4 complex based on the small-angle X-ray scattering analysis.

Original languageEnglish
Pages (from-to)289-307
Number of pages19
JournalJournal of Molecular Biology
Issue number2
StatePublished - Jan 18 2019

Bibliographical note

Publisher Copyright:
© 2018 Elsevier Ltd


  • Mycobacterium tuberculosis
  • PE–PPE proteins
  • protein export
  • small-angle X-ray scattering

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Molecular Biology


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