STRUCTURAL CHARACTERIZATION OF F-BAR DOMAINS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 几乎每个细胞过程中的关键事件的调节-从细胞信号传导到靶向蛋白质降解或DNA修复-需要改变效应蛋白的位置或活性的特定分子间相互作用。现在很清楚，这些相互作用中的大多数是由一个或多个结合“结构域”或“模块”驱动的，它们单独或协同工作以定义特定蛋白质的分子识别特性。也有几类结构域结合膜磷脂而不是（或除了）蛋白质靶标。特别是，一些膜靶向模块识别细胞膜中的特异性磷酸肌醇，并在细胞信号传导、膜运输、细胞骨架组织和其他细胞功能中发挥重要作用。F-BAR结构域已被称为结合（或感知）弯曲膜的结构域，并且我们发现酵母Rho-GAP Rgd 1 p具有PtdIns（4，5）P2特异性F-BAR结构域。本研究旨在通过提供任何BAR/F-BAR结构域家族成员与脂质结合靶标复合的第一个结构视图来解决PtdIns（4，5）P2识别的机制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Regulation of key events in almost every cellular process - from cell signaling to targeted protein degradation or DNA repair - requires specific intermolecular interactions that alter the location or activity of effector proteins. It is now clear that most of these interactions are driven by one or more binding 'domains' or 'modules', which work alone or in concert to define the molecular recognition properties of a particular proteins. There are also several classes of domain that bind membrane phospholipids instead of (or in addition to) protein targets. In particular, a few membrane-targeting modules recognize specific phosphoinositides in cellular membranes, and play an important role in cellular signaling, membrane trafficking, cytoskeletal organization, and other cellular functions. F-BAR domains have become known as domains the bind (or sense) curved membranes, and we have found that the yeast Rho-GAP Rgd1p has a PtdIns(4,5)P2-specific F-BAR domain. This research is designed to address the mechanism of PtdIns(4,5)P2 recognition by providing the first structural view of any BAR/F-BAR domain family member in complex with a lipid binding target.