Protein interaction evolution from promiscuity to specificity with reduced flexibility in an increasingly complex network.
Protein interaction evolution from promiscuity to specificity with reduced flexibility in an increasingly complex network.
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DOI：
10.1038/srep44948
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发表时间：
2017-03-24
影响因子：
4.6
通讯作者：
Geuten K
中科院分区：
文献类型：
--
作者：
Alhindi T;Zhang Z;Ruelens P;Coenen H;Degroote H;Iraci N;Geuten K
关于蛋白质进化的一个关键问题是蛋白质如何适应它们发挥功能的动态环境，以及它们的进化如何反过来塑造蛋白质相互作用网络。我们使用现存的和复活的祖先植物MADS结构域转录因子来了解SEPALLATA 3是如何进化和参与网络组织的，SEPALLATA 3是一种具有枢纽和胶水特性的蛋白质。虽然二聚体相互作用的密度在网络中饱和，但在全基因组三倍化事件后，许多新的相互作用由SEPALLATA 3介导。通过在不同年龄的二聚体网络之间交换SEPALLATA 3及其祖先，我们发现该蛋白失去了混杂相互作用的能力，并在进化中获得了特异性。这是伴随着限制构象通过脯氨酸残基的积累，这使得蛋白质的灵活性较低。另一方面，由于C-末端结构域插入，短营养相（非枢纽）能够获得蛋白质-蛋白质相互作用，从而允许更大的相互作用界面。这些研究结果表明，蛋白质相互作用的演变发生在构象动力学的水平上，当结合机制涉及诱导适合或构象选择。当蛋白质相互作用网络的复杂性需要特异性时，蛋白质可以朝着增加特异性而降低灵活性的方向进化。
A key question regarding protein evolution is how proteins adapt to the dynamic environment in which they function and how in turn their evolution shapes the protein interaction network. We used extant and resurrected ancestral plant MADS-domain transcription factors to understand how SEPALLATA3, a protein with hub and glue properties, evolved and takes part in network organization. Although the density of dimeric interactions was saturated in the network, many new interactions became mediated by SEPALLATA3 after a whole genome triplication event. By swapping SEPALLATA3 and its ancestors between dimeric networks of different ages, we found that the protein lost the capacity of promiscuous interaction and acquired specificity in evolution. This was accompanied with constraints on conformations through proline residue accumulation, which made the protein less flexible. SHORT VEGETATIVE PHASE on the other hand (non-hub) was able to gain protein-protein interactions due to a C-terminal domain insertion, allowing for a larger interaction interface. These findings illustrate that protein interaction evolution occurs at the level of conformational dynamics, when the binding mechanism concerns an induced fit or conformational selection. Proteins can evolve towards increased specificity with reduced flexibility when the complexity of the protein interaction network requires specificity.