NONRANDOM UNFOLDED STATES AND PROTEIN STABILITY

描述：这个研究项目的目标是寻求一个更大的 对非随机性结构的意义的理解 蛋白质的未折叠状态有助于蛋白质的稳定性和折叠。FK506 结合蛋白(FKBP)提供了一种独特的系统来识别这种 关联性。晶体和晶体中FKBP的高分辨结构 解的形式是可用的，并且FKBP的平衡展开具有 已经用各种光谱和光谱进行了彻底的表征 生化方法。此外，还对FKBP的结构进行了详细的研究 在浓缩尿素和盐酸胍中展开 执行，演示关联的非随机结构的存在 有特定的残留物。中非随机结构的位置 未折叠的FKBP与在 折叠的形式，并与倾向于 从统计和分析预测螺旋构象和转角构象 热力学尺度下的二级结构预测。另一方面 另一方面，这些初步研究的一个特别令人惊讶的发现是 在褶皱和展开中形成不同的次级结构 C-末端残基的状态。诱变和光谱技术 将结合各种方法来进一步描述展开的形式 并详细探讨这些关系。 折叠与展开的结构和热力学研究进展 FKBP将被用来理解非随机结构在 去折叠状态对FKBP的折叠和稳定性起着重要作用。角色 在改变FKBP的本征状态稳定性方面的非随机结构将 确定其他蛋白质中相似结构的一般规则。在……里面 此外，破译了热力学驱动力 折叠时C-末端残基的构象转换将 在蛋白质设计和三维结构中有意义 预测。

DESCRIPTION: The objective of this research program is to seek a greater understanding of the significance of non-random structure present in the unfolded states of proteins for protein stability and folding. The FK506 binding protein (FKBP) provides a unique system to identify such correlations. High resolution structures of FKBP in both the crystal and solution forms are available and the equilibrium unfolding of FKBP has been thoroughly characterized using a variety of spectroscopic and biochemical methods. In addition, a detailed structural study of FKBP unfolded in concentrated urea and guanidine hydrochloride has been performed, demonstrating the presence of non-random structure associated with specific residues. The location of the non-random structure in unfolded FKBP was correlated with similar structures observed in the folded form, and was more strongly correlated with the propensity for helical and turn conformations predicted from statistical and thermodynamic scales of secondary structure prediction. On the other hand, a particularly surprising finding from these initial studies was that different secondary structures are formed in the folded and unfolded states for the C-terminal residues. Mutagenesis and spectroscopic approaches will be combined to further characterize the unfolded form of FKBP and to explore these relationships in detail. The previous structural and thermodynamic studies of folded and unfolded FKBP will be used to understand the role that non-random structure in the unfolded state plays in the folding and stability of FKBP. The role of non-random structures in altering native state stability in FKBP will identify general rules for similar structures in other proteins. In addition, deciphering the thermodynamic driving forces responsible for the conformational switch in the C-terminal residue upon folding will have implications in protein design and in three dimensional structure prediction.