Minor D L, Kim P S
Department of Chemistry, Massachusetts Institute of Technology, Nine Cambridge Centre 02142.
Nature. 1994 Feb 17;367(6464):660-3. doi: 10.1038/367660a0.
Several model systems have been used to evaluate the alpha-helical propensities of different amino acids. In contrast, experimental quantitation of beta-sheet preferences has been addressed in only one model system, a zinc-finger peptide. 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 terminal stabilities of these proteins leads to a thermodynamic scale for beta-sheet propensities that spans a range of approximately 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.
已有多种模型系统用于评估不同氨基酸的α-螺旋倾向。相比之下，仅在一种模型系统——锌指肽中对β-折叠偏好进行了实验定量。在此，我们在富含β-折叠的小的、单体的、来自蛋白G的IgG结合结构域的变体中，测量了20种天然存在的氨基酸形成β-折叠的相对倾向。在β-折叠溶剂暴露表面的一个客体位点进行了氨基酸替换。使用了几个标准来确定这些突变不会引起显著的结构变化：与IgG的Fc结构域结合、量热展开和核磁共振光谱。对这些蛋白质末端稳定性的表征得出了一个β-折叠倾向的热力学尺度，对于天然存在的氨基酸（不包括脯氨酸），其范围约为2千卡/摩尔。差异的大小表明β-折叠偏好可能是蛋白质稳定性的重要决定因素。
