7npv
MycP5-free ESX-5 inner membrane complex, State II
Structural highlights
FunctionECCB5_MYCTU An ATPase (shown for residues 80-506) (PubMed:26396239). Part of the ESX-5 specialized secretion system, which is responsible for the secretion of EsxN and a number of PE_PGRS and PPE proteins, including PPE41.[1] [2] [3] Publication Abstract from PubMedMycobacterium tuberculosis is the cause of one of the most important infectious diseases in humans, which leads to 1.4 million deaths every year(1). 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(2,3). 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(5) protease. A trimer of MycP(5) caps a central periplasmic dome-like chamber that is formed by three EccB(5) dimers, with the proteolytic sites of MycP(5) facing towards the cavity. This chamber suggests a central secretion and processing conduit. Complexes without MycP(5) show disruption of the EccB(5) periplasmic assembly and increased flexibility, which highlights the importance of MycP(5) for complex integrity. Beneath the EccB(5)-MycP(5) chamber, dimers of the EccC(5) ATPase assemble into three bundles of four transmembrane helices each, which together seal the potential central secretion channel. Individual cytoplasmic EccC(5) 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. Structure and dynamics of a mycobacterial type VII secretion system.,Bunduc CM, Fahrenkamp D, Wald J, Ummels R, Bitter W, Houben ENG, Marlovits TC Nature. 2021 May;593(7859):445-448. doi: 10.1038/s41586-021-03517-z. Epub 2021 , May 12. PMID:33981042[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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