CRYSTALLOGRAPHIC STUDIES OF GI1-ALPHA MUTANTS

GI1-α 突变体的晶体学研究

• 批准号: 7955200
• 负责人: THOMAS P SAKMAR
• 金额: $ 0.43万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955200
• 关键词: Binding; Biological Assay; Cells; Computer Retrieval of Information on Scientific Projects Database; Drug Delivery Systems; Funding; G-Protein Signaling Pathway; G-Protein-Coupled Receptors; G-substrate; GTP-Binding Protein alpha Subunits; GTP-Binding Proteins; Grant; Guanine Nucleotides; In Vitro; Institution; Nucleotides; Protein Activation Pathway; Reporting; Research; Research Personnel; Resources; Signal Transduction; Source; Structure; United States National Institutes of Health; base; genetic regulatory protein; insight; interest; mutant; protein complex; receptor; structural biology

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. Heterotrimeric guanine nucleotide-binding regulatory proteins, G proteins relay signals from heptahelical transmembrane G protein coupled receptors (GPCRs) to the cellular interior. GPCRs activate G proteins by inducing the release of GDP from the G¿ subunit in the activated receptor-protein complex. Despite reports of many crystals structures of various G¿ subunits, we still lack a detailed understanding of the mechanism of receptor activated nucleotide exchange by the G¿ subunit. Our project is aimed at elucidating transient steps in the G protein activation pathway. Our general strategy is to obtain crystal structures of G protein mutants that we characterized in vitro and in cell-based assays. In particular, we have identified and characterized an interesting class of mutant G protein alpha subunits with extremely high basal rates of GDP release. These studies are very important to understanding the mechanism of action of various GPCR-targeted drugs and will help us to gain more structural insights into G protein signaling pathways in general.

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。 异源三聚体鸟嘌呤核苷酸结合调节蛋白，G蛋白将信号从七螺旋跨膜G蛋白偶联受体（GPCR）传递到细胞内部。GPCR通过诱导GDP从活化的受体-蛋白质复合物中的G亚基释放来活化G蛋白。尽管报道了许多不同G <$亚基的晶体结构，但我们仍然缺乏对G <$亚基受体激活核苷酸交换机制的详细了解。我们的项目旨在阐明G蛋白激活途径中的瞬时步骤。我们的一般策略是获得晶体结构的G蛋白突变体，我们的特点是在体外和细胞为基础的测定。特别是，我们已经确定并表征了一类有趣的突变G蛋白α亚基，其具有极高的GDP释放基础速率。 这些研究对于理解各种GPCR靶向药物的作用机制非常重要，并将帮助我们从总体上获得对G蛋白信号通路的更多结构见解。