Structure of the mycobacterial ESX-5 type VII secretion system membrane complex by single-particle analysis

Katherine S. H. Beckham, Luciano Ciccarelli, Catalin M. Bunduc, Haydyn D. T. Mertens, Roy Ummels, Wolfgang Lugmayr, Julia Mayr, Mandy Rettel, Mikhail M. Savitski, Dmitri I. Svergun, W. Bitter, Matthias Wilmanns, Thomas C. Marlovits, Annabel H. A. Parret, Edith N. G. Houben

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Mycobacteria are characterized by their impermeable outer membrane, which is rich in mycolic acids 1. To transport substrates across this complex cell envelope, mycobacteria rely on type VII (also known as ESX) secretion systems 2. In Mycobacterium tuberculosis, these ESX systems are essential for growth and full virulence and therefore represent an attractive target for anti-tuberculosis drugs 3. However, the molecular details underlying type VII secretion are largely unknown, due to a lack of structural information. Here, we report the molecular architecture of the ESX-5 membrane complex from Mycobacterium xenopi determined at 13â ...Å resolution by electron microscopy. The four core proteins of the ESX-5 complex (EccB 5, EccC 5, EccD 5 and EccE 5) assemble with equimolar stoichiometry into an oligomeric assembly that displays six-fold symmetry. This membrane-associated complex seems to be embedded exclusively in the inner membrane, which indicates that additional components are required to translocate substrates across the mycobacterial outer membrane. Furthermore, the extended cytosolic domains of the EccC ATPase, which interact with secretion effectors, are highly flexible, suggesting an as yet unseen mode of substrate interaction. Comparison of our results with known structures of other bacterial secretion systems demonstrates that the architecture of type VII secretion system is fundamentally different, suggesting an alternative secretion mechanism.

Original languageEnglish
Article number17047
Pages (from-to)1-7
Number of pages7
Issue number6
Early online date10 Apr 2017
Publication statusPublished - Jun 2017


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