Structural basis for recognition of the translocated intimin receptor (Tir) by intimin from enteropathogenic Escherichia coli

Intimin is a bacterial adhesion molecule involved in intimate attachment of enteropathogenic and enterohaemorrhagic Escherichia coli to mammalian host cells. Intimin targets the translocated intimin receptor (Tir), which is e xported by the bacteria and integrated into the host cell plasma membrane. In this study we localized the Tir-binding region of intimin to the C-termi nal 190 amino acids (Int190), We have also determined the region's high-res olution solution structure, which comprises an immunoglobulin domain that i s intimately coupled to a novel C-type lectin domain, This fragment, which is necessary and sufficient for Tir interaction, defines a new super domain in intimin that exhibits striking structural similarity to the integrin-bi nding domain of the Yersinia invasin and C-type lectin families, The extrac ellular portion of intimin comprises an articulated rod of immunoglobulin d omains extending from the bacterium surface, conveying a highly accessible 'adhesive tip' to the target cell. The interpretation of NMR-titration and mutagenesis data has enabled us to identify, for the first time, the bindin g site for Tir, which is located at the extremity of the Int190 moiety.