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所有细胞都至关重要。信号识别颗粒（SRP）及其受体（SR）构成介导大约三分之一的细胞蛋白质的共翻译靶向的主要细胞机制， 真核内质网或细菌质膜。尽管对SRP通路的研究取得了快速进展，但其分子机制的许多基本方面仍有待阐明。我们的总体目标是在生物化学和生物物理水平上破译这个普遍保守的靶向机器的复杂内部运作。我们的具体目标是破译的分子机制，通过该负载的货物蛋白的SRP耦合到其快速交付和有效的卸载到易位机器，并开始理解的背景下，拥挤的环境中的核糖体出口网站的SRP的机制。为此，我们设想了三个目标：（1）我们将破译SRP RNA在介导货物与SRP和SR GTP酶之间的通讯中的作用：（2）我们将阐明货物蛋白从靶向转移到易位机器的精确机制;（3）我们将阐明主要的共翻译分子伴侣（触发因子）是否以及如何调节SRP途径的效率和保真度。最终，这些研究不仅将推进我们对蛋白质在细胞内定位过程的理解，还将提供新的见解 在基础水平上的分子识别和调节的一般原则。拟议的研究是一个最基本的性质，并将有助于我们在分子水平上对所有活细胞的生理学和病理学的一般理解。