Blanco F J, Serrano L, Forman-Kay J D
EMBL, Meyerhofstrasse 1, Heidelberg, D69012, Germany.
J Mol Biol. 1998 Dec 11;284(4):1153-64. doi: 10.1006/jmbi.1998.2229.
The structures of the denatured states of the spectrin SH3 domain and a mutant designed to have a non-native helical tendency at the N terminus have been analyzed under mild acidic denaturing conditions by nuclear magnetic resonance methods with improved resolution. The wild-type denatured state has little residual structure. However, the denatured state of the mutant has an approximately 50% populated helical structure from residues 2 to 14, a region that forms part of the beta-sheet structure in the folded state. Comparison with a peptide corresponding to the same sequence shows that the helix is stabilized in the whole domain, likely by non-local interactions with other parts of the protein as suggested by changes in a region far from the mutated sequence. These results demonstrate that high populations of non-native secondary structure elements in the denatured state are compatible with the formation of the native folded structure.
在温和酸性变性条件下，利用分辨率更高的核磁共振方法，分析了血影蛋白SH3结构域的变性状态结构以及一个设计为在N端具有非天然螺旋倾向的突变体的结构。野生型变性状态几乎没有残余结构。然而，该突变体的变性状态在2至14位残基处具有约50%的螺旋结构，该区域在折叠状态下形成β-折叠结构的一部分。与对应相同序列的肽段比较表明，该螺旋在整个结构域中是稳定的，可能是通过与蛋白质其他部分的非局部相互作用，这一点由远离突变序列区域的变化所表明。这些结果表明，变性状态下高比例的非天然二级结构元件与天然折叠结构的形成是相容的。
