Many bacteria have developed sophisticated mechanisms of protein transport across membranes. These macromolecular secretory systems play a pivotal role in microbial pathogenesis and are considered as promising targets for a new generation of anti-bacterial therapy. The ESX systems of Mycobacterium tuberculosis, an important human pathogen, secrete multiple proteins that are implicated in host-pathogen interactions. The homologous secretion systems have been also identified in a number of Gram-positive pathogenic bacteria including Staphylococcus aureus and Bacillus anthracis. Although numerous components of the ESX systems have been identified, the structure of individual building blocks, the overall architecture of the system and the molecular mechanism of secretion are currently unknown. Our research aims to unravel the molecular mechanism of the ESX secretion system using structural biology methods, mainly X-ray crystallography and electron microscopy, in combination with biochemical and biophysical analyses. The ultimate goal of our research is to develop novel tuberculosis therapies.
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Tuukkanen AT, Freire D, Chan S, Arbing MA, Reed RW, Evans TJ, Zenkeviciutė G, Kim J, Kahng S, Sawaya MR, Chaton CT, Wilmanns M, Eisenberg D, Parret AHA, Korotkov KV. Structural variability of EspG chaperones from mycobacterial ESX-1, ESX-3, and ESX-5 Type VII Secretion Systems. (2019) Journal of Molecular Biology 431(2): 289-307. PMID: 30419243 PDB: 5VBA, 5DLB, 4L4W, 4RCL, 5SXL