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Biological and Structural Diversity of Type IV Secretion Systems

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  • Authors: Yang Grace Li1, Bo Hu2, Peter J. Christie3
  • Editors: Maria Sandkvist4, Eric Cascales5, Peter J. Christie6
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Microbiology and Molecular Genetics, McGovern Medical School, Houston, TX 77030; 2: Department of Microbiology and Molecular Genetics, McGovern Medical School, Houston, TX 77030; 3: Department of Microbiology and Molecular Genetics, McGovern Medical School, Houston, TX 77030; 4: Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan; 5: CNRS Aix-Marseille Université, Mediterranean Institute of Microbiology, Marseille, France; 6: Department of Microbiology and Molecular Genetics, McGovern Medical School, Houston, Texas
  • Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.PSIB-0012-2018
  • Received 17 August 2018 Accepted 08 February 2019 Published 05 April 2019
  • Peter J. Christie, [email protected]
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  • Abstract:

    The bacterial type IV secretion systems (T4SSs) are a functionally diverse superfamily of secretion systems found in many species of bacteria. Collectively, the T4SSs translocate DNA and monomeric and multimeric protein substrates to bacterial and eukaryotic cell types. T4SSs are composed of two large subfamilies, the conjugation machines and the effector translocators that transmit their cargoes through establishment of direct donor-target cell contacts, and a third small subfamily capable of importing or exporting substrates from or to the milieu. This review summarizes recent mechanistic and structural findings that are shedding new light on how T4SSs have evolved such functional diversity. Translocation signals are now known to be located C terminally or embedded internally in structural folds; these signals in combination with substrate-associated adaptor proteins mediate the docking of specific substrate repertoires to cognate VirD4-like receptors. For the Dot/Icm system, recent work has elucidated the structural basis for adaptor-dependent substrate loading onto the VirD4-like DotL receptor. Advances in definition of T4SS machine structures now allow for detailed comparisons of nanomachines closely related to the VirB/VirD4 T4SS with those more distantly related, e.g., the Dot/Icm and Cag T4SSs. Finally, it is increasingly evident that T4SSs have evolved a variety of mechanisms dependent on elaboration of conjugative pili, membrane tubes, or surface adhesins to establish productive contacts with target cells. T4SSs thus have evolved extreme functional diversity through a plethora of adaptations impacting substrate selection, machine architecture, and target cell binding.

  • Citation: Li Y, Hu B, Christie P. 2019. Biological and Structural Diversity of Type IV Secretion Systems. Microbiol Spectrum 7(2):PSIB-0012-2018. doi:10.1128/microbiolspec.PSIB-0012-2018.

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/content/journal/microbiolspec/10.1128/microbiolspec.PSIB-0012-2018
2019-04-05
2019-11-22

Abstract:

The bacterial type IV secretion systems (T4SSs) are a functionally diverse superfamily of secretion systems found in many species of bacteria. Collectively, the T4SSs translocate DNA and monomeric and multimeric protein substrates to bacterial and eukaryotic cell types. T4SSs are composed of two large subfamilies, the conjugation machines and the effector translocators that transmit their cargoes through establishment of direct donor-target cell contacts, and a third small subfamily capable of importing or exporting substrates from or to the milieu. This review summarizes recent mechanistic and structural findings that are shedding new light on how T4SSs have evolved such functional diversity. Translocation signals are now known to be located C terminally or embedded internally in structural folds; these signals in combination with substrate-associated adaptor proteins mediate the docking of specific substrate repertoires to cognate VirD4-like receptors. For the Dot/Icm system, recent work has elucidated the structural basis for adaptor-dependent substrate loading onto the VirD4-like DotL receptor. Advances in definition of T4SS machine structures now allow for detailed comparisons of nanomachines closely related to the VirB/VirD4 T4SS with those more distantly related, e.g., the Dot/Icm and Cag T4SSs. Finally, it is increasingly evident that T4SSs have evolved a variety of mechanisms dependent on elaboration of conjugative pili, membrane tubes, or surface adhesins to establish productive contacts with target cells. T4SSs thus have evolved extreme functional diversity through a plethora of adaptations impacting substrate selection, machine architecture, and target cell binding.

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Image of FIGURE 1
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.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.PSIB-0012-2018
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Image of FIGURE 2
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 ( 78 ). 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 ( 16 ). 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. ( 58 ). The DotL-adaptor receptor complex was not part of the visualized Dot/Icm T4SS ( 16 ) 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.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.PSIB-0012-2018
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