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: 8373184
• 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/8373184
• 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. PUBLIC HEALTH RELEVANCE: Proper localization of proteins is essential for all cells. Mislocalization of proteins cause impaired cell growth, function, and eventually cell death, leading to devastating diseases such as cystic fibrosis, diabetes, and neurodegeneration. The proposed studies will significantly advance our understanding of the mechanism of membrane protein localization and biogenesis within the cell, and contribute profoundly to our general understanding of physiology and pathology of all living cells at a molecular level.

描述（由申请人提供）：蛋白质的适当定位对所有细胞都至关重要。信号识别颗粒（SRP）及其受体（SR）构成了主要的细胞机制，介导大约三分之一的细胞蛋白的共翻译靶向