MEASUREMENT OF THE BETA-SHEET-FORMING PROPENSITIES OF AMINO-ACIDS
MEASUREMENT OF THE BETA-SHEET-FORMING PROPENSITIES OF AMINO-ACIDS
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DOI：
10.1038/367660a0
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发表时间：
1994-02-17
期刊：
影响因子：
64.8
通讯作者：
KIM, PS
中科院分区：
文献类型：
--
作者：
MINOR, DL;KIM, PS
几个模型系统已用于评估不同氨基酸的α-螺旋倾向（1-7）。相比之下，仅在一个模型系统（锌指肽）中解决了β折叠偏好的实验定量（8）。在这里，我们测量了来自G蛋白的小的、单体的、富含β折叠的IgG结合结构域的变体中的20种天然存在的氨基酸形成β折叠的相对倾向。氨基酸取代是在客体位点上的溶剂暴露的表面的β-折叠。使用几个标准来确定突变不会引起显著的结构变化：与IgG的Fc结构域的结合、量热解折叠和NMR光谱。这些蛋白质的热稳定性的表征导致β-折叠倾向的热力学标度，其跨越天然存在的氨基酸（不包括脯氨酸）的类似于2 kcal mol（-1）的范围。差异的大小表明，β折叠的偏好可能是蛋白质稳定性的重要决定因素。
SEVERAL model systems have been used to evaluate the alpha-helical propensities of different amino acids(1-7). In contrast, experimental quantitation of beta-sheet preferences has been addressed in only one model system, a zinc-finger peptide(8). Here we measure the relative propensity for beta-sheet formation of the twenty naturally occurring amino acids in a variant of the small, monomeric, beta-sheet-rich, IgG-binding domain from protein G. Amino-acid substitutions were made at a guest site on the solvent-exposed surface of the beta-sheet. Several criteria were used to establish that the mutations did not cause significant structural changes: binding to the Fc domain of IgG, calorimetric unfolding and NMR spectroscopy. Characterization of the thermal stabilities of these proteins leads to a thermodynamic scale for beta-sheet propensities that spans a range of similar to 2 kcal mol(-1) for the naturally occurring amino acids, excluding proline. The magnitude of the differences suggests that beta-sheet preferences can be important determinants of protein stability.