7NPT

Cytosolic bridge of an intact ESX-5 inner membrane complex

This is a non-PDB format compatible entry.

Summary for 7NPT

• Entry DOI: 10.2210/pdb7npt/pdb
• Related: 7NP7 7NPR 7NPS
• EMDB information: 12514 12517 12518 12519 12520
• Descriptor: ESX-5 secretion system protein EccC5, ESX-5 secretion system protein EccD5 (2 entities in total)
• Functional Keywords: t7ss, mycobacteria, protein transport, secretion, type vii secretion system, membrane, membrane protein
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv); More
• Total number of polymer chains: 3
• Total formula weight: 259862.56

Authors

Fahrenkamp, D.,Bunduc, C.M.,Wald, J.,Ummels, R.,Bitter, W.,Houben, E.N.G.,Marlovits, T.C. (deposition date: 2021-02-28, release date: 2021-05-26, Last modification date: 2024-07-10)

Primary citation

Bunduc, C.M.,Fahrenkamp, D.,Wald, J.,Ummels, R.,Bitter, W.,Houben, E.N.G.,Marlovits, T.C.
Structure and dynamics of a mycobacterial type VII secretion system.
Nature, 593:445-448, 2021

PubMed Abstract: Mycobacterium tuberculosis is the cause of one of the most important infectious diseases in humans, which leads to 1.4 million deaths every year. Specialized protein transport systems-known as type VII secretion systems (T7SSs)-are central to the virulence of this pathogen, and are also crucial for nutrient and metabolite transport across the mycobacterial cell envelope. Here we present the structure of an intact T7SS inner-membrane complex of M. tuberculosis. We show how the 2.32-MDa ESX-5 assembly, which contains 165 transmembrane helices, is restructured and stabilized as a trimer of dimers by the MycP protease. A trimer of MycP caps a central periplasmic dome-like chamber that is formed by three EccB dimers, with the proteolytic sites of MycP facing towards the cavity. This chamber suggests a central secretion and processing conduit. Complexes without MycP show disruption of the EccB periplasmic assembly and increased flexibility, which highlights the importance of MycP for complex integrity. Beneath the EccB-MycP chamber, dimers of the EccC ATPase assemble into three bundles of four transmembrane helices each, which together seal the potential central secretion channel. Individual cytoplasmic EccC domains adopt two distinctive conformations that probably reflect different secretion states. Our work suggests a previously undescribed mechanism of protein transport and provides a structural scaffold to aid in the development of drugs against this major human pathogen.

PubMed: 33981042
DOI: 10.1038/s41586-021-03517-z

Experimental method

ELECTRON MICROSCOPY (3.27 Å)