Novel Pathways of Membrane Protein Insertion

膜蛋白插入的新途径

• 批准号: 7734852
• 负责人: Ramanujan S Hegde
• 金额: $ 30.59万
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7734852
• 关键词: ATP phosphohydrolase; Biological; C-terminal; Cell Death; Cellular Membrane; Client; Complex; Future; Goals; Mediating; Membrane; Membrane Proteins; Molecular; N-terminal; Organism; Pathway interactions; Process; Proteins; Range; Reaction; Regulation; Role; Tail; Transmembrane Domain; intracellular protein transport; novel; protein transport; reconstitution; trafficking

Recently, we discovered a cytosolic TMD recognition complex (TRC) that selectively interacts with TA proteins destined for the ER membrane. A central component of TRC was identified as a highly conserved 40 kD ATPase and represents the first molecular factor in this widely used membrane protein insertion pathway (2). Other components that collaborate with TRC40 to mediate selective recognition, targeting, and insertion of TA proteins into the ER are unknown. We are now taking various approaches to identify these additional factor(s) and reconstitute the targeting reaction for TA proteins with defined components. Achieving these goals will define the core machinery and functions for a fundamental protein trafficking pathway and pave the way for future mechanistic and structural analyses.

最近，我们发现了一种胞质TMD识别复合物（TRC），该复合物（TRC）与原始的ER膜的TA蛋白有选择地相互作用。 TRC的中心成分被确定为高度保守的40 kD ATPase，代表了这种广泛使用的膜蛋白插入途径中的第一个分子因子（2）。与TRC40合作以介导选择性识别，靶向和插入TA蛋白的其他组件是未知的。现在，我们正在采用各种方法来识别这些其他因素，并重建具有定义成分的TA蛋白的靶向反应。实现这些目标将定义基本蛋白质运输途径的核心机械和功能，并为未来的机械和结构分析铺平道路。