STRUCTURAL STUDIES OF CDC42 MEDIATED CELLULAR TRANSFORMATION

CDC42介导的细胞转化的结构研究

• 批准号: 7598529
• 负责人: RICHARD A. CERIONE
• 金额: $ 2.39万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7598529
• 关键词: Area; Binding; Cellular biology; Clathrin-Coated Vesicles; Coat Protein Complex I; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Endocytosis; Funding; GTP-Binding Proteins; Grant; Growth Factor Receptors; Human; Institution; Laboratories; Malignant - descriptor; Mediating; Modeling; Molecular; Numbers; Play; Proteins; Publishing; Research; Research Personnel; Resolution; Resources; Role; Signal Pathway; Signal Transduction; Source; Structure; United States National Institutes of Health; Vesicle; Yeasts; base; interest; metaplastic cell transformation; ras-Related G-Proteins; receptor; trafficking

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. 1.Structures of signaling complexes relevant to the actions of Cdc42: A major emphasis of our laboratory has been directed at understanding how GTP-binding proteins act as molecular switches in cell signaling pathways. One area of emphasis has been the Ras-related GTP-binding protein, Cdc42, which is one of the most highly conserved GTP-binding proteins from yeast to humans. Cdc42 has been shown to play a number of fundamentally important roles in cell biology. The hyper-activation of Cdc42 leads to malignant transformation. This involves a Cdc42-mediated signaling pathway that regulates the signaling lifetime and trafficking of growth factor receptors. In particular, the binding of activated Cdc42 to the g coatomer (gCOP) subunit, which is part of a multi-protein complex that coats trafficking vesicles, is essential for this trafficking function. We have been interested in determining how activated Cdc42 binds to the g-coatomer subunit and how g-coatomer engages associated subunits of the COPI complex to participate in the assembly of trafficking vesicles. Recently, we have published the structure for the amino-terminal half of the g-coatomer subunit to 2.1 angstrom resolution, based on data that we collected at MacCHESS (see Hoffman et al., below). This has allowed us to propose a model regarding how COPI trafficking vesicles assemble. Remarkably, it appears that the assembly of the COPI complex is similar to the assembly of the adaptor complexes that direct the formation of clathrin-coated vesicles and receptor endocytosis.

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。 1.与Cdc 42的作用相关的信号传导复合物的结构： 我们实验室的一个主要重点是了解GTP结合蛋白如何作为细胞信号通路中的分子开关。 一个重点领域是Ras相关的GTP结合蛋白Cdc 42，它是从酵母到人类最高度保守的GTP结合蛋白之一。 cdc 42在细胞生物学中扮演着重要的角色。 Cdc 42的过度活化导致恶性转化。 这涉及Cdc 42介导的信号传导途径，其调节生长因子受体的信号传导寿命和运输。 特别是，激活的Cdc 42的g coatomer（gCOP）亚基，这是一个多蛋白复合物的一部分，涂层运输囊泡的结合，是必不可少的这种运输功能。 我们一直有兴趣确定如何激活Cdc 42结合到g-外被体亚基和如何g-外被体从事相关的COPI复合物的亚基参与组装的贩运囊泡。 最近，基于我们在MacCHESS收集的数据，我们已经公布了g-外被体亚基氨基末端一半的结构，分辨率为2.1埃（参见霍夫曼et al.，下面）。 这使我们能够提出一个关于COPI贩运囊泡如何组装的模型。 值得注意的是，似乎COPI复合物的组装类似于指导网格蛋白包被的囊泡和受体内吞作用形成的衔接子复合物的组装。