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  • Type IV secretion systems: ...
    Costa, Tiago R. D.; Harb, Laith; Khara, Pratick; Zeng, Lanying; Hu, Bo; Christie, Peter J.

    Molecular microbiology, March 2021, Volume: 115, Issue: 3
    Journal Article

    Bacterial type IV secretion systems (T4SSs) are a functionally diverse translocation superfamily. They consist mainly of two large subfamilies: (i) conjugation systems that mediate interbacterial DNA transfer and (ii) effector translocators that deliver effector macromolecules into prokaryotic or eukaryotic cells. A few other T4SSs export DNA or proteins to the milieu, or import exogenous DNA. The T4SSs are defined by 6 or 12 conserved “core” subunits that respectively elaborate “minimized” systems in Gram‐positive or ‐negative bacteria. However, many “expanded” T4SSs are built from “core” subunits plus numerous others that are system‐specific, which presumptively broadens functional capabilities. Recently, there has been exciting progress in defining T4SS assembly pathways and architectures using a combination of fluorescence and cryoelectron microscopy. This review will highlight advances in our knowledge of structure–function relationships for model Gram‐negative bacterial T4SSs, including “minimized” systems resembling the Agrobacterium tumefaciens VirB/VirD4 T4SS and “expanded” systems represented by the Helicobacter pylori Cag, Legionella pneumophila Dot/Icm, and F plasmid‐encoded Tra T4SSs. Detailed studies of these model systems are generating new insights, some at atomic resolution, to long‐standing questions concerning mechanisms of substrate recruitment, T4SS channel architecture, conjugative pilus assembly, and machine adaptations contributing to T4SS functional versatility. Type IV secretion systems (T4SSs) are a functionally diverse superfamily of translocation nanomachines deployed by most species of bacteria. Collectively, T4SSs mediate the transfer of mobile genetic elements or protein toxins to other bacteria, or effector proteins or other macromolecules to eukaryotic cells to aid in infection. Recent structural and fluorescence approaches are generating exciting new insights into how T4SSs assemble in the cell envelope and recruit and translocate substrates to other cells.