Mechanism and structure of the bacterial type IV secretion systems

• Published in: Biochimica et biophysica acta 2014-08, Vol.1843 (8), p.1578-1591
• Main Authors: Christie, Peter J., Whitaker, Neal, González-Rivera, Christian
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphatases - chemistry; Adenosine Triphosphatases - metabolism; Agrobacterium tumefaciens - genetics; Bacterial Secretion Systems - genetics; Conjugation; DNA - chemistry; DNA - metabolism; DNA transfer; Fimbriae, Bacterial - chemistry; Fimbriae, Bacterial - metabolism; Gram-Negative Bacteria - chemistry; Gram-Negative Bacteria - metabolism; Pathogenesis; Periplasmic Proteins - chemistry; Periplasmic Proteins - secretion; Pilus; Protein Binding; Protein Folding; Protein translocation; Protein Transport - genetics; Traffic ATPase
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/j.bbamcr.2013.12.019

The bacterial type IV secretion systems (T4SSs) translocate DNA and protein substrates to bacterial or eukaryotic target cells generally by a mechanism dependent on direct cell-to-cell contact. The T4SSs encompass two large subfamilies, the conjugation systems and the effector translocators. The conjugation systems mediate interbacterial DNA transfer and are responsible for the rapid dissemination of antibiotic resistance genes and virulence determinants in clinical settings. The effector translocators are used by many Gram-negative bacterial pathogens for delivery of potentially hundreds of virulence proteins to eukaryotic cells for modulation of different physiological processes during infection. Recently, there has been considerable progress in defining the structures of T4SS machine subunits and large machine subassemblies. Additionally, the nature of substrate translocation sequences and the contributions of accessory proteins to substrate docking with the translocation channel have been elucidated. A DNA translocation route through the Agrobacterium tumefaciens VirB/VirD4 system was defined, and both intracellular (DNA ligand, ATP energy) and extracellular (phage binding) signals were shown to activate type IV-dependent translocation. Finally, phylogenetic studies have shed light on the evolution and distribution of T4SSs, and complementary structure-function studies of diverse systems have identified adaptations tailored for novel functions in pathogenic settings. This review summarizes the recent progress in our understanding of the architecture and mechanism of action of these fascinating machines, with emphasis on the ‘archetypal’ A. tumefaciens VirB/VirD4 T4SS and related conjugation systems. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey. •We review structural information about bacterial type IV secretion systems (T4SSs).•We discuss adaptations to type IV machines that evolved for specialized functions.•We summarize functions of subunits and subassemblies of archetypal T4SSs.•We review mechanisms for substrate presentation to the bacterial T4SSs.•We present models depicting the substrate translocation route through T4SSs.