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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。我们将收集四种不同蛋白质系统晶体的x射线衍射数据：前列腺特异性膜抗原（PSMA）细胞外区、聚合免疫球蛋白受体（pIgR）、单纯疱疹病毒（HSV） gE-gI/Fc三元复合物及其组分、抗聚谷氨酰胺（Gln） Fab与含聚谷氨酰胺肽K2Q10K2络合。PSMA是一种180kda二聚体糖蛋白，主要表达于前列腺上皮细胞表面。前列腺癌显像剂Prostascint与PSMA结合。PSMA的结构可能有助于开发针对PSMA的前列腺癌治疗药物。pIgR是Ig超家族的一员，在分泌性上皮细胞的基底外表面结合IgA或IgM，并将其运输到根尖表面，作为粘膜表面的第一道防线。gE/gI-Fc复合物存在于病毒粒子和感染细胞的表面，可能对HSV的免疫逃避很重要。抗聚谷氨酰胺Fab与生物素化肽K2Q10K2复合物的结构将提供对聚谷氨酰胺重复序列构象的深入了解，这与包括亨廷顿病在内的多种神经系统疾病有关。目前还没有这四个系统的结构信息。SSRL的高强度晶体学光束线对于许多这些系统的本地数据收集是必不可少的，因为晶体在光束线处衍射到更高的分辨率（例如PSMA高达2¿¿更好）。大型探测器与小振荡的收集相结合，可以分离PSMA、pIgR、gE-gI/Fc和NgE/gI晶体长单元边缘的反射。最后，可调谐的光束线允许使用固有锌或硫原子，硒取代蛋白质或重原子衍生物的SAD和MAD相位方法。

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.