Correlated mutations contain information about protein-protein interaction
Correlated mutations contain information about protein-protein interaction
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DOI：
10.1006/jmbi.1997.1198
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发表时间：
1997-08-29
影响因子：
5.6
通讯作者：
Valencia, A
中科院分区：
文献类型：
--
作者：
Pazos, F;HelmerCitterich, M;Valencia, A
许多蛋白质已经进化形成特定的分子复合物，这种相互作用的特异性对于它们的功能至关重要。因此，必要的残基间接触网络必须在某种程度上限制蛋白质序列。换句话说，相互作用蛋白质的序列必须反映这种适应过程的结果。可以合理地假设，一个相互作用蛋白在进化过程中积累的序列变化必须通过另一个相互作用蛋白的变化来补偿。在这里，我们应用了一种方法来检测一组相互作用蛋白结构域的多个序列比对中的相关变化，并表明两个相互作用分子中以相关方式发生变化的位置往往靠近蛋白质-蛋白质界面。这使得开发一种仅从序列中预测残基接触对的方法成为可能。这种方法不需要了解相互作用蛋白质的结构，因此与传统的对接方法相比，它是完全不同的，并且适用范围更广。我们确实在这里证明，有关相关序列变化的信息足以在双域蛋白质的许多错误替代方案中挑选出正确的域间对接解决方案。在一种情况（血红蛋白）中也使用了相同的方法，其中我们尝试预测两种不同蛋白质而不是两个蛋白质结构域的界面。最后，我们在这里报告了仅基于序列信息的热休克蛋白 Hsc70 的域间接触区域的预测。 (C) 1997 学术出版社有限公司。
Many proteins have evolved to form specific molecular complexes and the specificity of this interaction is essential for their function. The network of the necessary inter-residue contacts must consequently constrain the protein sequences to some extent. Ln other words, the sequence of an interacting protein must reflect the consequence of this process of adaptation. It is reasonable to assume that the sequence changes accumulated during the evolution of one of the interacting proteins must be compensated by changes in the other.Here we apply a method for detecting correlated changes in multiple sequence alignments to a set of interacting protein domains and show that positions where changes occur in a correlated fashion in the two interacting molecules tend to be close to the protein-protein interfaces. This leads to the possibility of developing a method for predicting contacting pairs of residues from the sequence alone. Such a method would not need the knowledge of the structure of the interacting proteins, and hence would be both radically different and more widely applicable than traditional docking methods.We indeed demonstrate here that the information about correlated sequence changes is sufficient to single out the right inter-domain docking solution amongst many wrong alternatives of two-domain proteins. The same approach is also used here in one case (haemoglobin) where we attempt to predict the interface of two different proteins rather than two protein domains. Finally, we report here a prediction about the inter-domain contact regions of the heat-shock protein Hsc70 based only on sequence information. (C) 1997 Academic Press Limited.