A De Novo Designed Coiled-Coil Peptide with a Reversible pH-Induced Oligomerization Switch
A De Novo Designed Coiled-Coil Peptide with a Reversible pH-Induced Oligomerization Switch
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DOI：
10.1016/j.str.2016.03.027
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发表时间：
2016-06-07
期刊：
影响因子：
5.7
通讯作者：
Andre, Ingemar
中科院分区：
文献类型：
--
作者：
Lizatovic, Robert;Aurelius, Oskar;Andre, Ingemar
蛋白质构象开关有许多有用的应用，但很难合理设计。在这里，我们展示了如何等能的能量景观的高阶卷曲螺旋可以使一个寡聚化开关的形成，通过插入一个单一的不稳定元素到一个稳定的计算设计的支架。我们描述了一种从头设计的肽，发现其在pH 8的平行对称五聚体和pH 6的反平行二聚体的三聚体之间切换。五聚体和六聚体之间的转变是由谷氨酸残基的质子化状态的变化引起的，在两种低聚体形式中具有高度上移的pK（a）值。剧烈的构象变化加上狭窄的pH范围，使肽序列的一个有吸引力的候选人引入到其他蛋白质的pH传感。结果突出了简单α螺旋自组装成各种结构状态的显着能力。
Protein conformational switches have many useful applications but are difficult to design rationally. Here we demonstrate how the isoenergetic energy landscape of higher-order coiled coils can enable the formation of an oligomerization switch by insertion of a single destabilizing element into an otherwise stable computationally designed scaffold. We describe a de novo designed peptide that was discovered to switch between a parallel symmetric pentamer at pH 8 and a trimer of antiparallel dimers at pH 6. The transition between pentamer and hexamer is caused by changes in the protonation states of glutamatic acid residues with highly upshifted pK(a) values in both oligomer forms. The drastic conformational change coupled with the narrow pH range makes the peptide sequence an attractive candidate for introduction of pH sensing into other proteins. The results highlight the remarkable ability of simple-alpha helices to self-assemble into a vast range of structural states.