Molecular basis of coiled-coil oligomerization-state specificity
Molecular basis of coiled-coil oligomerization-state specificity
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DOI：
10.1073/pnas.1008502107
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发表时间：
2010-11-16
影响因子：
11.1
通讯作者：
Kammerer, Richard A.
中科院分区：
文献类型：
--
作者：
Ciani, Barbara;Bjelic, Sasa;Kammerer, Richard A.
卷曲螺旋如今被广泛且成功地用于合理地设计多股结构，用于包括基础研究、生物技术、纳米技术、材料科学和医学的应用。这些结构在几乎所有生物过程中的广泛应用以及重要功能突出了对控制卷曲螺旋折叠和寡聚化的因素的详细理解的需要。在这里，我们解决的重要和未解决的问题，为什么特定的寡聚化状态的决定因素内的卷曲螺旋的存在往往不与其拓扑结构。我们发现了一个意想不到的，一般的卷曲螺旋寡聚化状态的特异性和触发序列，卷曲螺旋的形成是必不可少的元素之间的联系。通过使用原型卷曲螺旋结构域的酵母转录激活因子GCN 4作为一个模型系统，我们表明，完善的三聚体特异性寡聚化状态的决定因素切换肽的拓扑结构从二聚体到三聚体只有当插入到触发序列。我们成功地证实了我们在另外两个不相关的卷曲螺旋二聚体，ATF 1和cortexillin-1。我们还表明，多个拓扑结构的决定因素可以共存于同一个触发序列，揭示了一个微妙的平衡所产生的寡聚状态的位置依赖的力量。我们的实验结果应显着提高卷曲螺旋的低聚状态的预测。因此，他们应该有重大影响的卷曲螺旋的合理设计，因此许多应用程序使用这些流行的寡聚域。
Coiled coils are extensively and successfully used nowadays to rationally design multistranded structures for applications, including basic research, biotechnology, nanotechnology, materials science, and medicine. The wide range of applications as well as the important functions these structures play in almost all biological processes highlight the need for a detailed understanding of the factors that control coiled-coil folding and oligomerization. Here, we address the important and unresolved question why the presence of particular oligomerization-state determinants within a coiled coil does frequently not correlate with its topology. We found an unexpected, general link between coiled-coil oligomerization-state specificity and trigger sequences, elements that are indispensable for coiled-coil formation. By using the archetype coiled-coil domain of the yeast transcriptional activator GCN4 as a model system, we show that well-established trimer-specific oligomerization-state determinants switch the peptide's topology from a dimer to a trimer only when inserted into the trigger sequence. We successfully confirmed our results in two other, unrelated coiled-coil dimers, ATF1 and cortexillin-1. We furthermore show that multiple topology determinants can coexist in the same trigger sequence, revealing a delicate balance of the resulting oligomerization state by position-dependent forces. Our experimental results should significantly improve the prediction of the oligomerization state of coiled coils. They therefore should have major implications for the rational design of coiled coils and consequently many applications using these popular oligomerization domains.