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Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Speaker Abstracts
34
Structural and Molecular Biology of Type IV Secretion Systems
Gabriel Waksman
.
Institute of Structural and Molecular Biology at UCL and Birkbeck, Malet Street, London,
WC1E 7HX, United Kingdom.
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 tumefaciens where it is naturally
responsible for the delivery of the T-DNA to the plant host-cell. The A. tumefaciens VirB/D
system comprises 12 proteins (VirB1 to 11 and VirD4). Recently, structures of large complexes
formed by several of these proteins have become available shedding unprecedented light on T4S
system secretion mechanism.
Key recent references
1- Chandran, R. Fronzes, S. Duquerroy, N. Cronin, J. Navaza, and G. Waksman (2009). Nature.
462:1011-1015.
2- R. Fronzes, E. Schaefer, H. Saibil, E. Orlova and G. Waksman (2009). Science. 323:266-268.
3- K. Wallden, R. Williams, J. Yan, P.W. Lian, L. Wang, K. Thalassinos, E.V. Orlova, and G.
Waksman (2012). Proc. Natl. Acad. Sci. USA. 109:11348-53.
4- H.H. Low, F. Gubellini, A. Rivera-Calzada, N. Braun, S. Connery, A. Dugeancourt, F. Lu, A.
Redzej, R. Fronzes, E.V. Orlova, and G. Waksman (2014). Nature. 508: 550–553.