Structure of the N-terminal domain of Yersinia pestis YopH at 2.0 angstromresolution

Yersinia pestis, the causative agent of bubonic plague, injects effector pr oteins into the cytosol of mammalian cells that enable the bacterium to eva de the immune response of the infected organism by interfering with eukaryo tic signal transduction pathways. YopH is a modular effector composed of a C-terminal protein tyrosine phosphatase (PTPase) domain and a multifunction al N-terminal domain that not only orchestrates the secretion and transloca tion of YopH into eukaryotic cells but also binds tyrosine-phosphorylated t arget proteins to mediate substrate recognition. The crystal structure of t he N-terminal domain of YopH (YopH(N); residues 1-130) has been determined at 2.0 Angstrom resolution. The aminoacid sequences that target YopH for se cretion from the bacterium and translocation into eukaryotic cells form int egral parts of this compactly folded domain. The structure of YopHN bears n o resemblance to eukaryotic phosphotyrosine-binding domains, nor is it remi niscent of any known fold. Residues that have been implicated in phosphotyr osine-dependent protein binding are clustered together on one face of YopHN , but the structure does not suggest a mechanism for protein-phosphotyrosin e recognition.