X-RAY CRYSTAL STUD NEDD4-2 UBIQUITIN PROTEIN LIGASE & PLASMID-ENCODED R67 DHFR

X 射线晶体螺柱 NEDD4-2 泛素蛋白连接酶

• 批准号: 7721287
• 负责人: NARENDRA NARAYANA
• 金额: $ 1.85万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721287
• 关键词: Blood Pressure; C2 Domain; Computer Retrieval of Information on Scientific Projects Database; DHFR gene; Deubiquitination; Dihydrofolate Reductase; Disease; Enzymes; Epithelial; Family; Funding; Grant; Human; Institution; Mutation; Phosphoric Monoester Hydrolases; Phosphorylation; Plasmids; Play; Proteins; Research; Research Personnel; Resources; Roentgen Rays; Role; Signal Transduction; Sodium Channel; Source; Structure; Syndrome; Ubiquitin-Protein Ligase Complexes; Ubiquitination; United States National Institutes of Health; X-Ray Crystallography; epithelial Na+ channel; extracellular; protein protein interaction; response; ubiquitin-protein ligase

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. Nedd4, a multi-modular protein belongs to a family of ubiquitin-protein ligases that is characterized by an amino terminal C2 domain, followed by 2-4 consecutive WW domains, and the carboxyl-terminal Hect domain. Nedd4 is known to target epithelial sodium channel (ENaC) for degradation. ENaC plays a major role in regulating blood pressure. ENaC mutations that disrupt the interaction with Nedd4 cause a human hypertensive disorder, Liddle's syndrome. Nedd4 WW domains are involved in the recognition of ENaC. Ubiquitination and phosphorylation have much in common: both occur rapidly  often in response to an extracellular signal  and both are quickly reversed by a large set of enzymes termed deubiquitination enzymes and phosphatases, respectively. It is clear that WW domains are ubiquitous protein modules and play fundamental role in protein-protein recognition. Aim: To understand specific protein-protein interactions in Nedd4 protein, we propose to determine the structure of the Nedd4 fragments by application of X-ray crystallography.

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。 Nedd 4是一种多模块蛋白，属于泛素蛋白连接酶家族，其特征在于氨基末端C2结构域，随后是2-4个连续的WW结构域和羧基末端Hect结构域。已知Nedd 4靶向上皮钠通道（ENaC）进行降解。ENaC在调节血压方面起着重要作用。破坏与Nedd 4相互作用的ENaC突变导致人类高血压疾病Liddle综合征。 Nedd 4 WW结构域参与ENaC的识别。泛素化和磷酸化有很多共同点：都发生得很快  通常是对细胞外信号的反应  这两种酶分别被称为去泛素化酶和磷酸酶的大量酶迅速逆转。很明显，WW结构域是普遍存在的蛋白质模块，在蛋白质-蛋白质识别中起着基础性作用。 目的：为了了解Nedd 4蛋白中特定的蛋白质-蛋白质相互作用，我们建议通过应用X射线晶体学来确定Nedd 4片段的结构。