The structure of the endogenous ESX-3 secretion system.

Poweleit, Nicole; Czudnochowski, Nadine; Nakagawa, Rachel; Trinidad, Donovan D; Murphy, Kenan C; Sassetti, Christopher M; Rosenberg, Oren S · Elife · 2019

basic_science · Level V

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Abstract

The ESX (or Type VII) secretion systems are protein export systems in mycobacteria and many Gram-positive bacteria that mediate a broad range of functions including virulence, conjugation, and metabolic regulation. These systems translocate folded dimers of WXG100-superfamily protein substrates across the cytoplasmic membrane. We report the cryo-electron microscopy structure of an ESX-3 system, purified using an epitope tag inserted with recombineering into the chromosome of the model organism <i>Mycobacterium smegmatis</i>. The structure reveals a stacked architecture that extends above and below the inner membrane of the bacterium. The ESX-3 protomer complex is assembled from a single copy of the EccB<sub>3</sub>, EccC<sub>3</sub>, and EccE<sub>3</sub> and two copies of the EccD<sub>3</sub> protein. In the structure, the protomers form a stable dimer that is consistent with assembly into a larger oligomer. The ESX-3 structure provides a framework for further study of these important bacterial transporters.

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