Nativelike structure in designed four α-helix bundles driven by buried polar interactions
Nativelike structure in designed four α-helix bundles driven by buried polar interactions
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DOI：
10.1021/ja064883r
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发表时间：
2006-11-15
影响因子：
15
通讯作者：
Dutton, P. Leslie
中科院分区：
文献类型：
--
作者：
Koder, Ronald L.;Valentine, Kathleen G.;Dutton, P. Leslie
我们发现，一个单一的内部极性相互作用，每个螺旋是足够的螺旋束蛋白的螺旋结构特异性。此外，我们使用不同形状的组氨酸结合辅因子直接结合到核心中，表明这种结构特异性不是规定的互补性的结果，“孔中的旋钮”核心包装。我们表明，我们可以通过连接辅因子，单独或成对地，结合一个或两个组氨酸配体，来打开和关闭单个螺旋的结构特异性。据我们所知，这是第一次证明这种广泛的操纵蛋白质结构的配体结合，一个重要的结果，普遍感兴趣的那些工作与自组装分子系统。最后，由于这些蛋白质的设计没有使用计算机建模，我们不仅证明了设计一个独特结构的辅因子结合蛋白并不像通常认为的那样困难，我们已经确定了为什么会这样：疏水核心互补性，这是非常困难的设计，是不必要的。相反，更简单的设计过程需要创建核心极性相互作用，这些相互作用本身可以驱动构象特异性。
We show that a single internal polar interaction per helix is sufficient to engender structural specificity in that helix in helical bundle proteins. Furthermore, we use histidine-binding cofactors of different shapes which bind directly into the core, demonstrating that this structural specificity is not the result of a prescribed complimentary, “knobs in holes” core packing. We show that we can switch structural specificity of individual helices on and off by ligating cofactors, singly and in pairs, which bind either one or two histidine ligands. To our knowledge, this is the first demonstration of such extensive manipulation of protein structure by ligand binding, an important result of general interest to those working with self-assembled molecular systems. Finally, as these proteins were designed without the use of computational modeling, we not only demonstrate that designing a uniquely structured cofactor binding protein is not as difficult as is generally believed, we have determined why this is so: hydrophobic core complementarity, which is very difficult to design, is not necessary. Instead, a much simpler design process entails the creation of core polar interactions which themselves can drive conformational specificity.