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Prof. Gabriel Waksman  

(Institute of Structural and Molecular Biology at UCL and Birkbeck, Malet Street, London)


Structural and Molecular Biology of Type IV Secretion System

Type IV secretion (T4S) systems are molecular machines used for the transport of macromolecules across the bacterial cell envelope. T4S systems are highly versatile. Conjugative T4S systems translocate DNA from a donor to a recipient bacterium and contribute to bacterial genome plasticity, spread of antibiotic resistance or other virulence trait among bacterial pathogens. In some bacteria such as Helicobacter pylori(Cag PI), Brucella suis(VirB/D), or Legionella pneumophila(Dot, Icm), T4S systems are directly involved in pathogenicity as they mediate the secretion of virulence factors (DNA or toxins) into host cells. The archetypal T4S system, the VirB/D system, was defined in Agrobacterium tumefacienswhere it is naturally responsible for the delivery of the T-DNA to the plant host-cell. Conjugative T4SS as well as the A. tumefaciensVirB/D system comprise 12 proteins (VirB1 to 11 and VirD4). Recently, structures of large complexes formed by several of these proteins and their substrates have become available for conjugative and protein translocation T4S systems shedding unprecedented light on T4S system secretion mechanism.