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Architecture of the mycobacterial type VII secretion system

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Abstract

Host infection by pathogenic mycobacteria such as Mycobacterium tuberculosis is facilitated by virulence factors secreted by type VII secretion systems1. Here we report the cryo-electron microscopy structure of a membrane-embedded core complex of the ESX-3/type VII secretion system from Mycobacterium smegmatis at 3.7 Å resolution. The core of the ESX-3 secretion machine consists of four protein components, EccB3:EccC3:EccD3:EccE3 in a 1:1:2:1 stoichiometry, building two identical protomers. The EccC3 coupling protein comprises a flexible array of four ATPase domains, which are linked to the membrane through a stalk domain. The ‘domain of unknown function’ (DUF) adjacent to the stalk is identified as an ATPase domain essential for secretion. EccB3 is predominantly periplasmatic but a small segment crosses the membrane and contacts the stalk domain, suggesting that conformational changes in the stalk domain triggered by substrate binding at the distal end of EccC3 and subsequent ATP hydrolysis in the DUF could be coupled to substrate secretion to the periplasm. Our results reveal that the architecture of type VII secretion systems differs markedly from other known secretion machines2.

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Author information

Correspondence to Oscar Llorca or Sebastian Geibel.

Supplementary information

Supplementary Tables 1-3

This file contains Supplementary Table 1 (Primers and oligonucleotides used for cloning), Supplementary Table 2 (Cryo-EM data collection, refinement and validation statistics) and Supplementary Table 3 (Correlation Coefficients (CC) after model refinement and fitting of homology models)

Reporting Summary

Supplementary Figure 1

This file contains the uncropped gels presented in the manuscript

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