Structure and Function of Telomerase Proteins

端粒酶蛋白的结构和功能

• 批准号: 1517625
• 负责人: Juli Feigon
• 金额: $ 158.83万
• 依托单位: University of California-Los Angeles
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1517625&HistoricalAwards=false
• 关键词: Structure; Function; Telomerase; Proteins

Telomerase is an enzyme complex that copies the DNA at the very ends of chromosomes and also protects the DNA from degradation. Without telomerase, chromosomes would get shorter every time they were copied (i.e. at every cell division). This project will investigate the structure, function, and dynamics of proteins in telomerase that are essential for its correct function. The project will advance understanding of cell aging and provide interdisciplinary training for graduate students and postdoctoral fellows in structural biology and biophysics. Encouragement to women and minorities to pursue careers in science will be pursued through outreach to high schools, by mentoring undergraduate students and postdoctoral fellows in research, and through the UCLA CityLab program. Telomerase is an RNA-protein complex (RNP) that functions as a specialized reverse transcriptase to extend the 3' ends of linear chromosomes and is a critical determinant of cellular aging and stem cell renewal. This research project will investigate the structure and function of telomerase accessory proteins in Tetrahymena using an integrative structural biology approach that combines NMR, X-ray crystallography, electron microscopy, and biochemical methods. The proposed structural studies will integrate existing information on telomerase and telomere binding proteins and provide new insights into assembly and interactions of the telomerase holoenzyme. The unified approach to structural biology used in this project will be applicable to the study of other protein complexes and RNPs.

端粒酶是一种酶复合物，它在染色体的末端复制DNA，并保护DNA免受降解。如果没有端粒酶，染色体在每次复制时（即每次细胞分裂时）都会变短。本计画将探讨端粒酶蛋白质的结构、功能与动力学，这些蛋白质对于端粒酶的正确功能是必不可少的。该项目将促进对细胞衰老的理解，并为结构生物学和生物物理学的研究生和博士后研究员提供跨学科培训。鼓励妇女和少数民族追求科学事业将通过推广到高中，通过指导本科生和博士后研究人员，并通过加州大学洛杉矶分校城市实验室计划。端粒酶是一种RNA-蛋白质复合物（RNP），其作为一种专门的逆转录酶发挥作用以延长线性染色体的3'末端，并且是细胞衰老和干细胞更新的关键决定因素。本研究计画将以核磁共振、X光晶体学、电子显微镜及生化学等方法，探讨四膜虫端粒酶辅助蛋白的结构与功能。建议的结构研究将整合现有的端粒酶和端粒结合蛋白的信息，并提供新的见解端粒酶全酶的组装和相互作用。本项目中使用的结构生物学的统一方法将适用于其他蛋白质复合物和RNP的研究。

项目成果

A structurally conserved human and Tetrahymena telomerase catalytic core

• DOI: 10.1073/pnas.2011684117
• 发表时间: 2020-11
• 期刊: Proceedings of the National Academy of Sciences
• 作者: Yaqiang Wang;M. Gallagher-Jones;L. Sušac;He Song;J. Feigon

Structure of S. pombe telomerase protein Pof8 C-terminal domain is an xRRM conserved among LARP7 proteins

• DOI: 10.1080/15476286.2020.1836891
• 发表时间: 2020-11-01
• 期刊: RNA BIOLOGY
• 影响因子: 4.1
• 作者: Basu, Ritwika;Eichhorn, Catherine D.;Feigon, Juli
• 通讯作者: Feigon, Juli