T-4 Lysozyme as a Model for Protein Folding

T-4 溶菌酶作为蛋白质折叠的模型

• 批准号: 8905322
• 负责人: Frederick Dahlquist
• 金额: $ 32.18万
• 依托单位: University of Oregon Eugene
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 1993-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8905322&HistoricalAwards=false
• 关键词: Lysozyme; Model; Protein; Folding

The goal of this project is to understand in greater detail the interrelationships of protein structure, stability and dynamics. T4 lysozyme is the protein used as a model. This moderate sized protein has a known 3-dimensional structure. Many mutant proteins of this lysozyme exist whose thermodynamic stability is modulated by the composition. Dr. Dahlquist has developed a plasmid expression system which allows large amounts of isotopically substituted protein to be produced efficiently. He will use modern nuclear magnetic resonance to study such proteins. The question of how proteins fold is acknowledged as one of the most important and least understood of modern molecular biology. A number of related areas would be greatly enhanced by the ability to understand in detail why a particular amino acid sequence folds into a particular shape and how changes in sequence change that shape, its thermodynamic stability and its interaction potential with other ligands. Progress in the understanding of the folding problem may allow more reliable predictions of structure from sequence data with a corresponding increase in the sophistication of engineered protein products.

这个项目的目标是更详细地了解蛋白质结构、稳定性和动力学之间的相互关系。T4溶菌酶是作为模型使用的蛋白质。这种中等大小的蛋白质具有已知的三维结构。这种溶菌酶存在许多突变蛋白，其热力学稳定性受其组成的调节。Dahlquist博士开发了一种质粒表达系统，它可以有效地生产大量同位素取代的蛋白质。他将使用现代核磁共振来研究这种蛋白质。蛋白质如何折叠的问题被认为是现代分子生物学中最重要、最不被理解的问题之一。如果能够详细了解特定氨基酸序列折叠成特定形状的原因，以及序列的变化如何改变该形状、其热力学稳定性以及它与其他配体的相互作用潜力，将极大地增强一些相关领域。在理解折叠问题方面的进展可能会使从序列数据中更可靠地预测结构成为可能，同时工程蛋白质产品的复杂性也会相应增加。