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bioRxiv · 10.1101/800169

A large inner membrane pore defines the ESX translocon

Poweleit, N.·Czudnochowski, N.·Nakagawa, R.·Murphy, K. C.·Sassetti, C. M.·Rosenberg, O.
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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; however, the architecture and mechanism of translocation has remained elusive. We report the cryo-electron microscopy structure of an ESX-3 system, purified using an epitope tag inserted with recombineering into the model organism Mycobacterium smegmatis. The structure reveals two large -helical membrane pores of sufficient diameter to secrete folded substrates. A complex, asymmetric, multimeric cytoplasmic domain is poised to gate and regulate the pores function. Our study provides mechanistic insights into the ESX systems and will guide structure-based design of drugs targeting this unique bacterial translocon.\n\nOne Sentence SummaryThe structure of the ESX-3 secretion system reveals a pore of sufficient size for the transit of folded substrates and a complex, cytoplasmic regulatory apparatus.

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Poweleit, N., Czudnochowski, N., Nakagawa, R., Murphy, K. C., Sassetti, C. M., Rosenberg, O.. 2019-10-10. A large inner membrane pore defines the ESX translocon. https://doi.org/10.1101/800169

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