This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Commensal bacteria have emerged as an important disease factor in human Crohn's disease (CD) and murine inflammatory bowel disease (IBD) models. it was recently reported that I2, a novel gene segment of microbial origin, is associated with human CD and that encodes a T-cell superantigen. Genomic cloning disclosed a locus containing the full-length I2 gene (pfiT) from Pseudomonas fluorescens. CD4+ T-cell responses to recombinant proteins were potent for I2 and pfiT. pfiT has several features of a virulence factor: association with an iron-response locus, restricted species distribution, and T-cell superantigen bioactivity. These findings suggest roles for pfiT and P. fluorescens in the pathogenesis of Crohn's disease. The current project is to determine the crystal structure of pfiT. Crystals of Se-Met substituted pfiT have been obtained. The best crystals diffracted to 1.9A resolution using an in-house X-ray system.
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