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

前列腺特异性膜抗原、PIGR、GE/GI-FC 和 ANTI-P 的结构

• 批准号: 7721777
• 负责人: Pamela J Bjorkman
• 金额: $ 0.08万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721777
• 关键词: Apical; Binding; Capromab Pendetide; Cells; Collection; Complex; Computer Retrieval of Information on Scientific Projects Database; Crystallography; Data; Data Collection; Development; Epithelial Cells; Funding; Glutamate Carboxypeptidase II; Glutamine; Glycoproteins; Grant; Huntington Disease; Immune; Immunoglobulin A; Immunoglobulin M; Institution; Malignant neoplasm of prostate; Methods; Molecular Conformation; Peptides; Phase; Polymeric Immunoglobulin Receptors; Proteins; Research; Research Personnel; Resolution; Resources; Simplexvirus; Source; Structure; Sulfur; Surface; Surface of the Prostate; System; United States National Institutes of Health; Virion; Zinc; beamline; cancer imaging; detector; extracellular; insight; member; nervous system disorder; polyglutamine; therapeutic target

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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）的胞外区、多聚免疫球蛋白受体（pIgR）、单纯疱疹病毒（HSV）gE-gI/Fc及其组分的三元复合物，以及与含聚谷氨酰胺（Gln）肽K2 Q10 K2复合的抗聚谷氨酰胺（Gln）Fab。 PSMA是主要在前列腺上皮细胞表面上表达的180 kDa二聚体糖蛋白。 前列腺癌显像剂Prostascint与PSMA结合。 PSMA的结构可能有助于靶向PSMA的前列腺癌治疗剂的开发。 pIgR是IG超家族的成员，结合分泌性上皮细胞基底外侧表面上的伊加或IgM，并将它们转运至顶端表面，作为粘膜表面的第一道防线。gE/gI-Fc复合物存在于病毒体和感染细胞的表面，可能对HSV的免疫逃避很重要。 与生物素化肽K2 Q10 K2复合的抗聚谷氨酰胺Fab的结构将提供对聚谷氨酰胺重复序列构象的深入了解，聚谷氨酰胺重复序列已涉及各种神经系统疾病，包括亨廷顿舞蹈症？的疾病。 目前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至关重要，因为晶体在光束线处具有更高的分辨率（例如，对于PSMA，高达2 ½）。 大型检测器与小振荡的收集相结合，允许从PSMA、pIgR、gE-gI/Fc和NgE/gI晶体的长晶胞边缘分离反射。 最后，可调谐光束线允许使用SAD和MAD定相方法，使用固有的锌或硫原子、硒取代的蛋白质或重原子衍生物。