@article{f687b6a3bd8640d18ce77082fa5c915a,
title = "Priming mycobacterial ESX-secreted protein B to form a channel-like structure",
abstract = "ESX-1 is a major virulence factor of Mycobacterium tuberculosis, a secretion machinery directly involved in the survival of the microorganism from the immune system defence. It disrupts the phagosome membrane of the host cell through a contact-dependent mechanism. Recently, the structure of the inner-membrane core complex of the homologous ESX-3 and ESX-5 was resolved; however, the elements involved in the secretion through the outer membrane or those acting on the host cell membrane are unknown. Protein substrates might form this missing element. Here, we describe the oligomerisation process of the ESX-1 substrate EspB, which occurs upon cleavage of its C-terminal region and is favoured by an acidic environment. Cryo-electron microscopy data shows that quaternary structure of EspB is conserved across slow growing species, but not in the fast growing M. smegmatis. EspB assembles into a channel with dimensions and characteristics suitable for the transit of ESX-1 substrates, as shown by the presence of another EspB trapped within. Our results provide insight into the structure and assembly of EspB, and suggests a possible function as a structural element of ESX-1.",
keywords = "Cryo-EM, EspB, ESX-1, Mycobacteria, Preferential orientation, VII SECRETION, CRYO-EM, OUTER-MEMBRANE, TUBERCULOSIS, SYSTEM, VIRULENCE, HELIX, ELECTROSTATICS, VISUALIZATION, TRANSLOCATION",
author = "A. Gijsbers and V. Vinciauskaite and A. Siroy and Y. Gao and G. Tria and A. Mathew and N. Sanchez-Puig and C. Lopez-Iglesias and P.J. Peters and R.B.G. Ravelli",
note = "Funding Information: We thank Paul van Schayck (UM) for indispensable SerialEM and IT support; the Microscopy CORE Lab (UM) for their technical and scientific support; Yue Zhang (UM) for model refinement support; Chris Lewis (UM) for tomogram reconstruction support; Florence Pojer and Stewart Cole (Global Health Institute, Lausanne, Switzerland) for initial sample aliquots and preliminary studies; Ron Heeren and Shane Ellis (UM) for native mass spectrometry support; and Hang Nguyen (UM) for critical reading of the manuscript. Nuria S{\'a}nchez-Puig acknowledges the support from the PASPA-DGAPA programme from UNAM and CONACYT 283909. This research received funding from the Netherlands Organisation for Scientific Research (NWO) in the framework of the Fund New Chemical Innovations, numbers 731.016.407 and 184.034.014, from the European Union's Horizon 2020 Research and Innovation Programme under Grant Agreement No 766970 Q-SORT. This research is also part of the M4I research programme supported by the Dutch Province of Limburg through the LINK programme. Funding Information: We thank Paul van Schayck (UM) for indispensable SerialEM and IT support; the Microscopy CORE Lab (UM) for their technical and scientific support; Yue Zhang (UM) for model refinement support; Chris Lewis (UM) for tomogram reconstruction support; Florence Pojer and Stewart Cole (Global Health Institute, Lausanne, Switzerland) for initial sample aliquots and preliminary studies; Ron Heeren and Shane Ellis (UM) for native mass spectrometry support; and Hang Nguyen (UM) for critical reading of the manuscript. Nuria S{\'a}nchez-Puig acknowledges the support from the PASPA-DGAPA programme from UNAM and CONACYT 283909. This research received funding from the Netherlands Organisation for Scientific Research (NWO) in the framework of the Fund New Chemical Innovations, numbers 731.016.407 and 184.034.014, from the European Union's Horizon 2020 Research and Innovation Programme under Grant Agreement No 766970 Q-SORT. This research is also part of the M4I research programme supported by the Dutch Province of Limburg through the LINK programme. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
doi = "10.1016/j.crstbi.2021.06.001",
language = "English",
volume = "3",
pages = "153--164",
journal = "Current Research in Structural Biology",
issn = "2665-928X",
publisher = "Elsevier B.V.",
}