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.

这项工作的广泛和长期目标是阐明 蛋白质折叠的规则 牛胰 选择胰蛋白酶抑制剂（BPTI）作为模型系统 因为它是一种简单的球状多肽， 大量的结构生物物理和理论数据是 已经可用于野生型蛋白质。 基本 重点将是大量生产转基因的 具有扰动折叠特性的BPTI形式， 从生物病理学角度来描述这些。 具体研究 优先事项是： 1)解决“设计出”二硫化物的问题 通过使BPTI突变体缺失两个或更多个 天然二硫化物。 2)促进合作者实验室在 所选BPTI突变体的结构和动力学。 这种结合遗传学和生物物理学的方法 一个非常简单的模型的折叠机构的解剖 蛋白质应该有助于阐明仍然知之甚少的 蛋白质折叠的过程。