Chapter 22 : Biological and Structural Diversity of Type IV Secretion Systems

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The bacterial type IV secretion systems (T4SSs) are a large, versatile family of macromolecular translocation systems functioning in Gram-negative (G) and Gram-positive (G) bacteria ( ). These systems mediate the transfer of DNA or monomeric or multimeric protein substrates to a large range of prokaryotic and eukaryotic cell types ( Fig. 1A ). Conjugation systems, the earliest described subfamily of T4SSs ( ), transfer mobile genetic elements (MGEs) between bacteria. They pose an enormous medical problem because MGEs often harbor cargoes of antibiotic resistance genes and fitness traits that endow pathogens with antibiotic resistance and other growth advantages under selective pressures ( ). Effector translocators, a more recently described T4SS subfamily ( ), are deployed by pathogenic bacteria to deliver effector proteins to eukaryotic cells during the course of infection ( ). The conjugation and effector translocator systems, as well as newly discovered interbacterial killing systems, transmit their cargos through direct donor-target cell contact ( ). A few other T4SSs designated uptake or release systems acquire DNA substrates from the milieu or release DNA or protein substrates into the milieu ( Fig. 1A ) ( ).

Citation: Li Y, Hu B, Christie P. 2019. Biological and Structural Diversity of Type IV Secretion Systems, p 277-289. In Sandkvist M, Cascales E, Christie P (ed), Protein Secretion in Bacteria. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PSIB-0012-2018
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Figure 1

Functional and compositional diversity of the bacterial type IV secretion systems (T4SSs). (Left) Contact-dependent conjugation systems and recently described killing systems deliver DNA or protein substrates directly to bacterial target cells. Contact-independent systems mediate DNA import, DNA export, or export of the multimeric pertussis toxin. (Right) Various pathogenic bacteria and symbionts have evolved T4SSs to deliver effector proteins or DNA-protein complexes into eukaryotic host cells to subvert host physiological processes. Gene arrangements and architectures of the VirB/VirD4 and Dot/Icm secretion systems, with color-coding of the genes encoding homologous subunits; unshaded genes are unique to the Dot/Icm system. The VirB/VirD4 subunit enzymatic functions and associations with inner membrane complex (IMC), outer membrane core complex (OMCC), or pilus are listed. PG Hydrolase, peptidoglycan hydrolase; T4CP, type IV coupling protein.

Citation: Li Y, Hu B, Christie P. 2019. Biological and Structural Diversity of Type IV Secretion Systems, p 277-289. In Sandkvist M, Cascales E, Christie P (ed), Protein Secretion in Bacteria. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PSIB-0012-2018
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Figure 2

Architectures of the phylogenetically distant VirB/VirD4 and Dot/Icm T4SSs. A schematic of the VirB structure elaborated by the Trw T4SS and solved by single-particle nsEM. A hexamer of the VirD4 receptor is fitted between the two hexameric barrels of the VirB4 ATPase. The VirD4 receptor recruits MGEs, such as conjugative plasmids, through recognition of components of the relaxosome (relaxase and accessory factors) assembled at the origin-of-transfer () sequence. VirD4 recruits protein substrates (colored dots) through direct or adaptor-mediated contacts. Substrates engage with the VirD4 receptor and are then delivered sequentially through a translocation channel composed of the VirB proteins listed at the right, as deduced from the transfer DNA immunoprecipitation assay ( ). The route of transfer across the IM is not known; substrates might be conveyed through the VirD4 hexamer (route 1, solid line), the VirB4 hexamer (route 2, small dashed line), or a channel composed of the VirB6 and VirB8 subunits (route 3, dotted line). Substrates then pass through the periplasm and across the OM via an OMCC channel. A schematic of the Dot/Icm T4SS solved by cryo-ET ( ). The centrally stacked hexamers of the VirB4-like DotO and DotB form the cytoplasmic entrance to a channel that spans the entire cell envelope. The bell-shaped DotL-adaptor complex is comprised of the hexameric nucleotide binding domain (purple) and C-terminal domain bound with DotN (brown), IcmS (yellow), IcmW (aqua), and LvgA (green); reprinted with permission by Kwak et al. ( ). The DotL-adaptor receptor complex was not part of the visualized Dot/Icm T4SS ( ) and is provisionally positioned adjacent to the Dot/Icm T4SS. Upon loading of substrates, the DotL-adaptor complex is postulated to present effectors to the DotB/DotO energy center for delivery through the central channel. Comparison of the R388-encoded VirB substructure and the Dot/Icm T4SS. A central section through the longitudinal plane of the VirB single-particle reconstruction with cross sections of the OMCC and IMC at the positions indicated. A central section through longitudinal plane of a global average structure of Dot/Icm T4SS with cross sections at the positions indicated. A three-dimensional (3D) surface rendering of the VirB substructure shown in side and bottom views. The side-by-side hexameric barrels of the VirB4 ATPase are colored pink. A 3D surface rendering of the Dot/Icm T4SS shown in side and bottom views. The bacterial membranes are in green and the DotO and DotB hexameric ATPases comprising the entrance to the translocation channel are in shades of pink and purple, respectively.

Citation: Li Y, Hu B, Christie P. 2019. Biological and Structural Diversity of Type IV Secretion Systems, p 277-289. In Sandkvist M, Cascales E, Christie P (ed), Protein Secretion in Bacteria. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PSIB-0012-2018
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