STRUCTURES OF PROSTATE SPECIFIC MEMBRANE ANTIGEN, PIGR, A GE/GI-FC AND AN ANTI-P

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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. We will collect x-ray diffraction data on crystals of four different protein systems: the extracellular region of prostate specific membrane antigen (PSMA), the polymeric immunoglobulin receptor (pIgR), a ternary complex of herpes simplex virus (HSV) gE-gI/Fc and its components, and an anti-poly-glutamine (Gln) Fab complexed with the poly-Gln containing peptide, K2Q10K2. PSMA is a 180 kDa dimeric glycoprotein expressed predominantly on the surfaces of prostate epithelial cells. Prostascint, a prostate cancer imaging agent, binds to PSMA. The structure of PSMA may aid the development of prostate cancer therapeutics that target PSMA. pIgR, a member of the Ig superfamily, binds IgA or IgM on the basolateral surface of secretory epithelial cells and transports them to the apical surface, serving as a first line of defense at the mucosal surfaces. The gE/gI-Fc complex is found on the surface of virions and infected cells and is likely important for immune evasion by HSV. The structure of the anti-poly-Gln Fab complexed with the biotinylated peptide K2Q10K2 will provide insight into the conformation of poly-Gln repeats, which have been implicated in a variety of neurological disorders including Huntington¿s Disease. There is currently no structural information available for any of these four systems. The high intensity crystallography beamlines at SSRL are essential for native data collection for many of these systems because the crystals diffract to higher resolution (e.g. up to 2 ¿ better for PSMA) at the beamline. The large detectors combined with the collection of small oscillations allow for the separation of reflections from long unit cell edges of PSMA, pIgR, gE-gI/Fc, and NgE/gI crystals. Lastly, the tunable beamlines allow for the use of SAD and MAD phasing methods using inherent zinc or sulfur atoms, selenenium-substituted proteins, or for heavy atom derivatives.