EAGER: Evolution of Beta Roll Peptides to Create Allosterically-Regulated Binding Domains Using Bacterial Cell Surface Display

EAGER：利用细菌细胞表面展示进化 Beta Roll 肽以创建变构调节的结合域

• 批准号: 1161160
• 负责人: Scott Banta
• 金额: $ 10.09万
• 依托单位: Columbia University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1161160&HistoricalAwards=false
• 关键词: EAGER; Evolution; Beta; Roll; Peptides

1161160/ BantaThe overall goal of this innovative and high risk NSF EAGER award, funded by the Biotechnology, Biochemical and Biomass Engineering Program and by the Biosensing Program, is to use directed evolution to modify novel calcium-regulated beta roll peptides so that they can bind to protein targets with built-in allosteric recognition. The beta roll peptide has a cork-screw structure that reversibly forms in the presence of calcium. This domain has not evolved to bind to other proteins, but structurally it resembles the leucine rich repeat and ankyrin repeat proteins, which have both evolved, and been engineered, for biomolecular recognition. The researchers have begun to use directed evolution to create new beta roll peptides that bind to a model protein target, and the built-in allosteric regulation of the scaffold will enable the binding interface to be formed depending on the calcium concentration. This will be the first example of the directed evolution of an intrinsically disordered peptide for biomolecular recognition. These peptides can then be used in sensing or other molecular engineering applications.

1161160/Banta这个创新和高风险的NSF EAGER奖的总体目标，由生物技术，生物化学和生物质工程计划和生物传感计划资助，是使用定向进化来修饰新型钙调节β卷肽，使它们可以结合到具有内置变构识别的蛋白质靶点。 β-roll肽具有软木塞螺旋结构，在钙的存在下可逆地形成。 这个结构域还没有进化到与其他蛋白质结合，但在结构上它类似于富含亮氨酸的重复序列和锚蛋白重复序列蛋白，这两种蛋白质都已经进化和工程化，用于生物分子识别。 研究人员已经开始使用定向进化来创建新的β卷肽，这些肽与模型蛋白质靶点结合，支架的内置变构调节将使结合界面能够根据钙浓度形成。 这将是第一个例子的定向进化的内在无序肽的生物分子识别。 然后，这些肽可以用于传感或其他分子工程应用。