title: IpaB-IpgC interaction defines binding motif for type III secretion translocator.
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 2 essential virulence factors of Shigella: invasion plasmid antigens (Ipa) B and C. Here, we report the 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 that is stabilized by conserved residues lining the cleft. Analysis of the cocrystal structure reveals a sequence motif that is functional in the IpaB translocator class from different bacteria as determined by isothermal titration calorimetry. Our results show how translocators are chaperoned and may allow the design of inhibitors of enterobacterial diseases.
authors.affiliation: Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Michele
authors.initials: M
authors.lastname: Lunelli
authors.forename: Ravi Kumar
authors.initials: RK
authors.lastname: Lokareddy
authors.forename: Arturo
authors.initials: A
authors.lastname: Zychlinsky
authors.forename: Michael
authors.initials: M
authors.lastname: Kolbe
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D012763:Shigella flexneri / Q000378:metabolism / Q000472:pathogenicity
chemical_list: D001426:Bacterial Proteins; D018832:Molecular Chaperones; C087447:ipaB protein, Shigella; C094580:IpgC protein, Shigella