STRUCTURE AND PLASTICITY OF PERIPHERAL MEMBRANE PROTEINS

外周膜蛋白的结构和可塑性

• 批准号: 7955188
• 负责人: Holger Sondermann
• 金额: $ 0.11万
• 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/7955188
• 关键词: Adaptor Signaling Protein; Affinity; Binding; Cell Surface Receptors; Cells; Cellular Membrane; Computer Retrieval of Information on Scientific Projects Database; Down-Regulation; Dynamin; Event; Funding; Grant; Housekeeping; Institution; Membrane; Membrane Protein Traffic; Membrane Proteins; Metabolism; Peripheral; Phospholipids; Process; Protein Binding; Protein Conformation; Proteins; Reaction; Research; Research Personnel; Resources; Shapes; Signal Transduction; Signaling Protein; Solutions; Sorting - Cell Movement; Source; Structure; United States National Institutes of Health; Vesicle; amphiphysin; cell motility; design; membrane model; nexin; preference; receptor recycling; 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. The presence of various domains in signaling proteins with affinity for phospholipids suggests that signaling reactions and protein conformations are likely to be modulated by membrane interactions. Cellular membranes are highly dynamic structures that change their shape during events such as vesicle budding and cell migration, and serve as signaling platforms during such processes. These cellular events are crucial for down-regulation of cell surface receptors, recycling of membrane proteins and many other housekeeping functions in cell metabolism and signaling. A binding module with preference for deformed membranes, the BAR (Bin-Amphiphysin-Rvs) domain, has been described only recently. This domain appears in the context of a large variety of multi-domain signaling proteins, and we speculate that membrane binding might alter the activities of neighboring domains and the overall conformation of these proteins. To get at the apo-state in the absence of membranes, we wish to determine the structures of multi-domain BAR domain-containing proteins, specifically focusing on Sorting nexin 9 and Endophilin. Both proteins are adaptor proteins that bind Dynamin and other proteins involved in membrane trafficking and fission. The structures will be used to design approaches that will allow us to study conformational changes and overall plasticity of these proteins in solution and on model membranes.

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。 在信号蛋白中存在对磷脂具有亲和力的各种结构域表明，信号反应和蛋白质构象可能受到膜相互作用的调节。细胞膜是高度动态的结构，其在诸如囊泡出芽和细胞迁移的事件期间改变其形状，并且在这些过程期间充当信号平台。这些细胞事件对于细胞表面受体的下调、膜蛋白的再循环以及细胞代谢和信号传导中的许多其他管家功能至关重要。一个结合模块与变形膜的偏好，BAR（Bin-Amphiphysin-Rvs）域，最近才被描述。该结构域出现在各种各样的多结构域信号蛋白的背景下，我们推测，膜结合可能会改变邻近结构域的活动和这些蛋白质的整体构象。为了在没有膜的情况下获得脱辅基状态，我们希望确定含有多结构域BAR结构域的蛋白质的结构，特别是集中在分选连接蛋白9和内啡肽。这两种蛋白质都是衔接蛋白，结合发动蛋白和其他参与膜运输和裂变的蛋白质。这些结构将用于设计方法，使我们能够研究这些蛋白质在溶液中和模型膜上的构象变化和整体可塑性。