This research is supported by the National Institutes of Health grant AI34501.
Nature Structural and Molecular Biology
Secretin, Cryomicroscopy, Bacterial proteins, Cholera toxin
The type II secretion system (T2SS) is a macromolecular complex spanning the inner and outer membranes of Gram-negative bacteria. Remarkably, the T2SS secretes folded proteins including multimeric assemblies like cholera toxin and heat-labile enterotoxin from Vibrio cholerae and enterotoxigenic Escherichia coli, respectively. The major outer membrane T2SS protein is the “secretin” GspD. Electron cryomicroscopy reconstruction of the V. cholerae secretin at 19 Å resolution reveals a dodecameric structure reminiscent of a barrel with a large channel at its center that appears to contain a closed periplasmic gate. The GspD periplasmic domain forms a vestibule with a conserved constriction, and binds to a pentameric exoprotein and to the trimeric tip of the T2SS pseudopilus. By combining our results with structures of the cholera toxin and T2SS pseudopilus, we provide a structural basis for a possible secretion mechanism of the T2SS.
Reichow, S. L., Korotkov, K. V., Hol, W. G., & Gonen, T. (2010). Structure of the cholera toxin secretion channel in its closed state. Nature structural & molecular biology, 17(10), 1226-1232.