Structures of EccB1 and EccD1 from the core complex of the mycobacterial ESX-1 type VII secretion system

Jonathan M. Wagner, Sum Chan, Timothy J. Evans, Sara Kahng, Jennifer Kim, Mark A. Arbing, David Eisenberg, Konstantin V. Korotkov

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Background: The ESX-1 type VII secretion system is an important determinant of virulence in pathogenic mycobacteria, including Mycobacterium tuberculosis. This complicated molecular machine secretes folded proteins through the mycobacterial cell envelope to subvert the host immune response. Despite its important role in disease very little is known about the molecular architecture of the ESX-1 secretion system. Results: This study characterizes the structures of the soluble domains of two conserved core ESX-1 components - EccB1 and EccD1. The periplasmic domain of EccB1 consists of 4 repeat domains and a central domain, which together form a quasi 2-fold symmetrical structure. The repeat domains of EccB1 are structurally similar to a known peptidoglycan binding protein suggesting a role in anchoring the ESX-1 system within the periplasmic space. The cytoplasmic domain of EccD1has a ubiquitin-like fold and forms a dimer with a negatively charged groove. Conclusions: These structures represent a major step towards resolving the molecular architecture of the entire ESX-1 assembly and may contribute to ESX-1 targeted tuberculosis intervention strategies.

Original languageEnglish
Article number5
JournalBMC Structural Biology
Issue number1
StatePublished - Feb 27 2016

Bibliographical note

Funding Information:
We thank Maksymilian Chruszcz, University of South Carolina, for assistance and advice on data processing. We thank the staff of the UCLA-DOE Institute Protein Expression Technology Center, supported by the U.S. Department of Energy, Office of Biological and Environmental Research (BER) program under Award Number DE-FC02-02ER63421, and the UCLA Crystallization Core for assistance in protein purification and crystallization screening. Authors thank staff members of beamline 24-ID-C, and Southeast Regional Collaborative Access Team (SER-CAT) at the Advanced Photon Source, Argonne National Laboratory, for assistance during data collection. Use of the Advanced Photon Source was supported by the U. S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. W-31-109-Eng-38. Work performed in the laboratory of D.E. is supported by the Howard Hughes Medical Institute and National Institutes of Health grants 23616-002-06 F3:02, TBSGC P01 (AI068135), and TBSGC P01 (AI095208). Research reported in this publication was partially supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant numbers P20GM103486 and P30GM110787, and by the National Institute of Allergy and Infectious Diseases grant number R01AI119022 to KVK.

Publisher Copyright:
© 2016 Wagner et al.


  • ESX
  • EccB
  • EccD
  • Mycobacterium tuberculosis
  • Type VII secretion system

ASJC Scopus subject areas

  • Structural Biology


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