The Biophysics of BPTI Folding Mutants

BPTI 折叠突变体的生物物理学

• 批准号: 9018707
• 负责人: Stephen Anderson
• 金额: $ 11.68万
• 依托单位: Rutgers University New Brunswick
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-03-15 至 1994-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9018707&HistoricalAwards=false
• 关键词: Biophysics; BPTI; Folding; Mutants

The broad, long-term objective of this work is to elucidate the rules that govern protein folding. Bovine pancreatic trypsin inhibitor (BPTI) has been chosen as a model system because it is a simple globular polypeptide, and a large amount of structural biophysical, and theoretical data is already available for the wild type protein. The basic thrust will be to produce, in quantity, genetically-modified forms of BPTI that have perturbed folding properties and characterize these biophysically. Specific Research priorities are: 1) Address the problem of "designing out" disulfide bonds by making BPTI mutants missing two or more of the native disulfides. 2) Facilitate work in collaborators' laboratories on the structure and dynamics of selected BPTI mutants. This combined genetic and biophysical approach to the dissection of the folding mechanism of a very simple model protein should help illuminate the still poorly-understood process of protein folding.

这项工作的广泛长期目标是阐明控制蛋白质折叠的规则。 牛胰腺胰蛋白酶抑制剂（BPTI）已被选择为模型系统，因为它是一种简单的球状多肽，并且大量结构性生物物理，并且理论数据已经可用于野生型蛋白质。 基本的推力将是用遗传改性的BPTI产生具有干扰折叠特性并以生物物理表征的BPTI的遗传改性形式。 具体的研究优先级是：1）通过使BPTI突变体缺少两个或多个天然二硫化物来解决“设计”二硫键的问题。 2）促进合作者实验室的工作，以了解选定的BPTI突变体的结构和动态。 这种非常简单的模型蛋白质的折叠机理解剖的结合遗传和生物物理方法应有助于照亮蛋白质折叠的较差过程。