Modulating repeat protein stability: The effect of individual helix stability on the collective behavior of the ensemble
Modulating repeat protein stability: The effect of individual helix stability on the collective behavior of the ensemble
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DOI：
10.1002/pro.638
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发表时间：
2011-06-01
期刊：
影响因子：
8
通讯作者：
Regan, Lynne
中科院分区：
文献类型：
--
作者：
Cortajarena, Aitziber L.;Mochrie, Simon G. J.;Regan, Lynne
重复序列蛋白是由一个小的结构基序串联而成的，其中三级结构通过重复序列内和相邻重复序列之间的相互作用而稳定。一些研究表明，这种模块化的结构是明显的模块化的热力学性质。具体而言，重复蛋白质的全局稳定性可以通过简单的线性模型来描述，仅考虑两个参数：单个重复单元的稳定性（H）和单元之间的耦合相互作用（J）。如果重复单元是相同的，则H和J的单个值连同重复单元的数目足以完全描述一系列中任何蛋白质的热力学行为。在这项工作中，我们演示了如何可以改变一个重复蛋白的全局稳定性，在一个可预测的方式，通过修改只有H参数。以先前表征的一系列共有三肽重复序列（TPR）（CTPRa）蛋白质为例，我们在基本重复单元中引入突变，使单个重复单元的稳定性增加，但其与相邻单元的相互作用不变。换句话说，我们增加了H，但保持J不变。我们证明了一系列这样的重复蛋白质的变性曲线可以拟合，并且可以通过一维伊辛模型预测额外的曲线，其中只有H从CTPRa系列的原始拟合改变。我们的研究结果表明，我们可以显着增加重复蛋白的稳定性，通过合理地增加单位（H），而重复（J）之间的相互作用保持不变。
Repeat proteins are tandem arrays of a small structural motif, in which tertiary structure is stabilized by interactions within a repeat and between neighboring repeats. Several studies have shown that this modular structure is manifest in modular thermodynamic properties. Specifically, the global stability of a repeat protein can be described by simple linear models, considering only two parameters: the stability of the individual repeated units (H) and the coupling interaction between the units (J). If the repeat units are identical, single values of H and J, together with the number of repeated units, is sufficient to completely describe the thermodynamic behavior of any protein within a series. In this work, we demonstrate how the global stability of a repeat protein can be changed, in a predictable fashion, by modifying only the H parameter. Taking a previously characterized series of consensus tetratricopeptide repeats (TPR) (CTPRa) proteins, we introduced mutations into the basic repeating unit, such that the stability of the individual repeat unit was increased, but its interaction with neighboring units was unchanged. In other words, we increased H but kept J constant. We demonstrated that the denaturation curves for a series of such repeat proteins can be fit and additional curves can be predicted by the one-dimensional Ising model in which only H has changed from the original fit for the CTPRa series. Our results show that we can significantly increase the stability of a repeat protein by rationally increasing the stability of the units (H), whereas the interaction between repeats (J) remains unchanged.