Molecular Mechanism of Protein Targeting by the Signal Recognition Particle

信号识别粒子靶向蛋白质的分子机制

• 批准号: 8731245
• 负责人: Shu-ou Shan
• 金额: $ 34.64万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-28 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8731245
• 关键词: Address; Affect; Binding; Biochemical; Biogenesis; Biological; Cell Death; Cell membrane; Cells; Cellular Membrane; Commit; Communication; Complex; Coupled; Crowding; Cues; Cystic Fibrosis; Decision Making; Diabetes Mellitus; Disease; Docking; Endoplasmic Reticulum; Ensure; Environment; Genome; Goals; Guanosine Triphosphate Phosphohydrolases; Investigation; Kinetics; Knowledge; Life; Maps; Measurement; Mediating; Membrane; Membrane Proteins; Modeling; Molecular; Molecular Chaperones; Movement; Nature; Nerve Degeneration; Pathology; Pathway interactions; Physiology; Process; Proteins; RNA; Reaction; Regulation; Research; Ribosomes; Role; Series; Signal Recognition Particle; Signal Transduction; Site; Specificity; Staging; Testing; Translations; Work; base; cell growth; driving force; insight; molecular recognition; polypeptide; prevent; receptor; research study; signal recognition particle receptor; single-molecule FRET; tool

DESCRIPTION (provided by applicant): Proper localization of proteins is crucial for all cells. The signal recognition particle (SRP) and its receptor (SR) constitute the major cellular machinery that mediates the co-translational targeting of roughly one third of cellular proteins to the eukaryotic endoplasmic reticulum, or the bacterial plasma membrane. Although rapid progress has been made in understanding the SRP pathway, many fundamental aspects of its molecular mechanism remain to be elucidated. Our general goal is to decipher, at a biochemical and biophysical level, the intricate inner workings of this universally conserved targeting machine. Our specific goal is to decipher the molecular mechanisms by which the loading of the cargo proteins on the SRP is coupled to its rapid delivery and efficient unloading to the translocation machinery, and to begin understand the mechanism of SRP in the context of the crowded environment at the ribosome exit site. To this end, three aims are envisioned: (1) We will decipher the role of the SRP RNA in mediating the communication between the cargo and the SRP and SR GTPases; (2) We will elucidate the precise mechanisms by which the cargo protein is transferred from the targeting to the translocation machinery; and (3) We will decipher whether and how the major co-translational chaperone, trigger factor, modulates the efficiency and fidelity of the SRP pathway. Ultimately, these studies will not only advance our understanding of the process of protein localization within the cell, but also provide new insights into the general principles of molecular recognition and regulation at a fundamental level. The proposed research is of a most basic nature, and will contribute profoundly to our general understanding of physiology and pathology of all living cells at the molecular level.

描述（由申请人提供）：蛋白质的正确定位对于所有细胞至关重要。信号识别粒子（SRP）及其受体（SR）构成了主要的细胞机制，它介导了大约三分之一的细胞蛋白的共同靶向靶向 真核生物内质网或细菌质膜。尽管在理解SRP途径方面取得了快速的进步，但其分子机制的许多基本方面仍有待阐明。我们的一般目标是在生化和生物物理水平上解密这种普遍保守的靶向机的复杂内部工作。我们的具体目标是破译分子机制，使SRP上货物蛋白的负载与其快速输送和有效的卸载机制结合到易位机械，并开始在拥挤的环境的上下文中理解SRP机制核糖体出口站点。为此，设想了三个目标：（1）我们将破译SRP RNA在介导货物与SRP和SR GTPases之间的通信中的作用； （2）我们将阐明将货物蛋白从靶向转移到易位机械的精确机制； （3）我们将破译主要的共同翻译伴侣触发因子是否以及如何调节SRP途径的效率和保真度。最终，这些研究不仅会提高我们对细胞中蛋白质定位过程的理解，而且还提供了新的见解。 在基本层面上的分子识别和调节的一般原则。拟议的研究具有最基本的性质，将对我们对分子水平所有活细胞的生理学和病理学的一般理解做出深远的贡献。