Expanding the Genetic Code with Phosphoserine

用磷酸丝氨酸扩展遗传密码

• 批准号: 0645283
• 负责人: Dieter Soll
• 金额: --
• 依托单位: Yale University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2010-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0645283&HistoricalAwards=false
• 关键词: Expanding; Genetic; Code; Phosphoserine

Synthesis of proteins containing amino acids outside of the genetic code has recently resurfaced as a topic of much interest and presents a great challenge intellectually and technically. Reprogramming the genetic code requires two key events: (i) The creation of a new efficient 'orthogonal' aminoacyl tRNA synthetase:tRNA pair able to generate solely a non canonical aminoacyl tRNA. (ii) The ability to specify the position in which this amino acid will be inserted in the protein by recoding a particular mRNA codon. Based on the natural existence of the recently discovered methanogen aminoacylsynthetase like protein, O-phosphoseryl tRNA synthetase and its cognate tRNACys research will be initiated to develop a prokaryotic and a eukaryotic system for the cotranslational insertion of phosphoserine at pre determined positions in a polypeptide based on the nonsense codon UAG in a messenger RNA. Given the importance of phosphoserine in eukaryotic proteins essential for cell proliferation, cellular signaling, and cell death, a robust method of making phosphoserine containing proteins will have wide application and great significance. This project will provide interdisciplinary training for undergraduate and postdoctoral students.

含有遗传密码之外的氨基酸的蛋白质的合成最近重新出现，作为一个非常感兴趣的话题，并提出了一个巨大的挑战，智力和技术。 重新编程遗传密码需要两个关键事件：（i）创建一个新的有效的“正交”氨酰tRNA合成酶：tRNA对，能够单独产生一个非规范的氨酰tRNA。(ii)通过重新编码特定的mRNA密码子来指定该氨基酸插入蛋白质的位置的能力。 基于最近发现的产甲烷菌氨酰合成酶样蛋白的天然存在，O-磷酸丝氨酸tRNA合成酶及其同源tRNACys的研究将开始开发基于信使RNA中无义密码子UAG的多肽中预定位置的磷酸丝氨酸共翻译插入的原核和真核系统。鉴于磷酸丝氨酸在细胞增殖、细胞信号传导和细胞死亡所必需的真核蛋白质中的重要性，制备含磷酸丝氨酸的蛋白质的稳健方法将具有广泛的应用和重大意义。 该项目将为本科生和博士后学生提供跨学科培训。