Oral Presentation 26th ACMM “2020 Visions in Microscopy”

Invited talk - In Situ Structures of Bacterial Secretion Systems by Electron Cryotomography (#114)

Debnath Ghosal 1 , Kwang Cheol Jeong 2 , Joseph P. Vogel 2 , Grant J. Jensen 1
  1. California Institute of Technology, PASADENA, CA, United States
  2. Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, US

Type IV secretion systems (T4SSs) are large macromolecular machines that translocate protein and DNA and are involved in the pathogenesis of multiple human diseases. We used complementary electron cryotomography and immunofluorescence microscopy to investigate the molecular architecture and biogenesis of the Dot/Icm type IVB secretion system (T4BSS) utilized by the human pathogen Legionella pneumophila. Our detailed structural analysis mapped the location of the core and accessory components of the Legionella core-transmembrane subcomplex revealing a well-ordered central channel that opens into a windowed large secretion chamber with an unusual symmetry. Exploiting these findings, we deciphered an early-stage assembly process that begins with targeting of Dot/Icm components to the bacterial poles. Polar targeting of this T4BSS is mediated by two Dot/Icm proteins, DotU and IcmF, that interestingly are homologs of the T6SS membrane complex components TssL and TssM, suggesting the Dot/Icm T4BSS is a hybrid system. Finally, in depth examination of the biogenesis pathway revealed that the Dot/Icm complex assembles by an innovative “outside-inside” mechanism.