The notion that protein function is allosterically regulated by structural or dynamic changes in proteins has been extensively investigated in several protein domains in isolation. In particular, PDZ domains have represented a paradigm for these studies, despite providing conflicting results. Furthermore, it is still unknown how the association between protein domains in supramodules, consitituting so-called supertertiary structures, affects allosteric networks. Here, we experimentally mapped the allosteric network in a PDZ:ligand complex, both in isolation and in the context of a supramodular structure, and show that allosteric networks in a PDZ domain are highly dependent on the supertertiary structure in which they are present. This striking sensitivity of allosteric networks to the presence of adjacent protein domains is likely a common property of supertertiary structures in proteins. Our findings have general implications for prediction of allosteric networks from primary and tertiary structures and for quantitative descriptions of allostery.

蛋白质的功能受蛋白质的结构或动态变化变构调节的观点已经在几个蛋白质域中进行了广泛的研究。特别是，PDZ域代表了这些研究的范例，尽管提供了矛盾的结果。此外，仍然未知的是，超模块中的蛋白质结构域之间的关联如何构成所谓的三级结构，会影响变构网络。在这里，我们以实验方式将PDZ：配体复合物中的变构网络进行了孤立和超模块结构的映射，并显示了PDZ域中的变构网络高度依赖于它们所在的超三级结构。变构网络对相邻蛋白质结构域的存在的这种惊人的敏感性可能是蛋白质上三级结构的共同特性。我们的发现对于从一级和三级结构预测变构网络以及对变构进行定量描述具有普遍意义。