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/ Bantathe这项创新和高风险NSF急切奖的总体目标是由生物技术，生物化学和生物量工程计划以及通过生物启用计划资助的，是使用定向进化来修改新颖的钙调控βRoll肽，以便与蛋白质靶向蛋白质靶标与内置的固定型识别结合。 β卷肽具有软木螺旋结构，该结构在钙的存在下可逆地形成。 该结构域尚未演变为与其他蛋白质结合，但是在结构上，它类似于浓密的亮氨酸重复蛋白，而脚踝重复蛋白既进化又经过了设计，又是为生物分子识别而设计的。 研究人员已经开始使用定向进化来创建与模型蛋白靶标结合的新β卷肽，并且支架的内置变构调节将使结合界面能够根据钙浓度形成。 这将是固有无序肽用于生物分子识别的定向演变的第一个例子。 然后，这些肽可以用于传感或其他分子工程应用中。