STRUCTURAL STUDIES OF THE HUMAN ESTROGEN RECEPTOR(HER): HER MUTANTS, HER COMP

人类雌激素受体（HER）的结构研究：她的突变体，她的比较

• 批准号: 7725994
• 负责人: GEOFFREY L GREENE
• 金额: $ 1.19万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7725994
• 关键词: Complex; Computer Retrieval of Information on Scientific Projects Database; Condition; DNA Binding Domain; Data; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogen Receptors; Funding; Glucocorticoid Receptor; Grant; Growth; Human; Individual; Institution; KLK3 gene; Ligand Binding Domain; Ligands; Nuclear Receptors; Orphan; Process; Protein Isoforms; Proteins; Purpose; Research; Research Personnel; Resources; Screening procedure; Series; Source; Structure; Therapeutic; United States National Institutes of Health; Work; estrophilin; mutant; novel; receptor; scaffold

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. The proposed project is part of our ongoing efforts to structurally characterize the human Estrogen Receptor (hER) and evaluate synthetic modulators of its activity for therapeutic purposes. In the past we have collected data at the APS on several complexes of the hER ligand binding domain (LBD) with novel ligands with unusual structural scaffolds that have variable efficacy on the two isoforms of hER. Under this new proposal, we will collect data on crystals of a series of hER deletion mutants encompassing its different domains. Here our emphasis is on the structural characterization of the hER protein in its entirety. To date, the only known structures of ER are those of its individual LBD and DBD (DNA binding domain). In addition, we will also characterize the crystal complexes of hER LBD and its various co-activator protein partners. In the past, we worked mostly with ERalpha but have since obtained crystals of ERbeta LBD in complex with various ligands as well as with other proteins. We have also initiated efforts on crystallizing other nuclear receptors including the Glucocorticoid receptor and novel orphan receptors with no known ligands. We have crystallized several of the above-mentioned proteins and are currently in the process of screening different crystal forms for diffraction quality and optimizing their growth conditions.

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。 拟议的项目是我们正在进行的努力的一部分，结构特征的人雌激素受体（hER）和评估其活性的合成调节剂的治疗目的。在过去，我们已经收集了数据在APS上的几个复合物的hER配体结合域（LBD）与新的配体具有不寻常的结构支架，具有可变的功效hER. Under这两个异构体的hER。在这个新的建议，我们将收集数据的晶体一系列的hER缺失突变体，包括其不同的域。在这里，我们的重点是在其整体的hER蛋白的结构表征。迄今为止，ER的唯一已知结构是其单独的LBD和DBD（DNA结合结构域）的结构。此外，我们还将表征hER LBD及其各种共激活蛋白伴侣的晶体复合物。在过去，我们主要研究ER α，但后来获得了与各种配体以及其他蛋白质复合的ER β LBD晶体。我们还开始努力结晶其他核受体，包括糖皮质激素受体和没有已知配体的新型孤儿受体。我们已经将上述几种蛋白质结晶化，目前正在筛选不同晶型的衍射质量并优化其生长条件。