Protein Structure and Folding at Low Temperature

了解蛋白质如何以及为什么折叠成其天然构象具有重要的生物学意义。尽管在这个问题上已经做了很多工作，但对这个过程的细节所知相对较少。芬克博士正在研究决定特定折叠途径和天然结构的因素。长期目标是学习多肽的氨基酸序列引导折叠路径到自然状态的“规则”。芬克博士将使用：1)分子不同区域的特定信号或探针来帮助确定蛋白质折叠和展开的顺序；2)位点特异性突变体，利用环境敏感探针在独特和选定的位点上促进蛋白质的形成，并探测单个氨基酸在折叠中的作用；3)在零度以下的温度和水-甲醇低温溶剂中，允许在展开和再折叠中稳定和表征部分折叠的中间体。

An understanding of how and why a protein folds into its native conformation is of major biological importance. Although much work has been done on this problem still relatively little is known about the details of the process. Dr. Fink is studying the factors which determine a particular folding pathway and hence native structure. The long-term goals are to learn the "rules" by which the amino acid sequence of a polypeptide guides the folding path to the native state. Dr. Fink will use: 1) specific signals or probes in different regions of the molecule to aid determining the order in which the protein folds and unfolds; 2) site-specific mutants to facilitate the formation of protein with environment-sensitive probes in unique and selected sites and probe the role of individual amino acids on the folding; and 3) subzero temperatures and aqueous-methanol cryosolvents to permit the stabilization and characterization of partially-folded intermediates in both unfolding and refolding.