Joint Research Group Macromolecular Crystallography
Structure of the month - July 2009
Proc. Natl. Acad. Sci. USA Vol. 106, 2009, Pages 9661-9666
IpaB-IpgC interaction defines binding motif for type III secretion translocator
Michele Lunelli*, Ravi Kumar Lokareddy*, Arturo Zychlinsky, and Michael Kolbe
Department of Cellular Microbiology, Max-Planck-Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany
Correspondence: kolbe@mpiib-berlin.mpg.de
* These authors contributed equally to this work
Abstract
The delivery of virulence factors into host cells through type III secretion systems is essential for enterobacterial pathogenesis. Molecular chaperones bind specifically to virulence factors in the bacterial cytosol before secretion. Invasion plasmid gene C (IpgC) is a chaperone that binds two essential virulence factors of Shigella: invasion plasmid antigens (Ipa) B and C. Here we report the first crystal structure of IpgC alone and in complex with the chaperone binding domain (CBD) of IpaB. The chaperone captures the CBD in an extended conformation which is stabilized by conserved residues lining the cleft. Analysis of the co-crystal structure reveals a sequence motif which is functional in the IpaB translocator class from different bacteria as determined by isothermal titration calorimetry (ITC). Our results show how translocators are chaperoned and may allow the design of inhibitors of enterobacterial diseases.
Reference
Proc Natl Acad Sci USA. 2009 Jun 16;106(24):9661-6.
Figure 1. IpgC forms a dimer in the crystal. Ribbon representation of the apo IpgC dimer found in the asymmetric unit with subunits colored in green and orange.
Figure 2. Surface representation of IpgC subunit B and a yellow stick representation for the IpaB CBD, as found in the cocrystal. The CBD occupies the major groove of IpgC in an extended conformation.
Table 1. Summary of data collections at BESSY for initial structure solution by SeMet-MAD