Department of Biology, KU Leuven, Leuven, Belgium.
Department of Pharmacy, University of Salerno, Salerno, Italy.
Sci Rep. 2017 Mar 24;7:44948. doi: 10.1038/srep44948.
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.
一个关于蛋白质进化的关键问题是蛋白质如何适应其功能的动态环境，以及它们的进化反过来如何塑造蛋白质相互作用网络。我们使用现存和复活的祖先植物 MADS 结构域转录因子来理解 SEPALLATA3（具有枢纽和粘性特性的蛋白质）是如何进化并参与网络组织的。尽管网络中二聚体相互作用的密度已经饱和，但在整个基因组三倍体事件之后，许多新的相互作用开始由 SEPALLATA3 介导。通过在不同年龄的二聚体网络之间交换 SEPALLATA3 和它的祖先，我们发现该蛋白质在进化过程中失去了杂乱无章的相互作用能力，获得了特异性。这伴随着脯氨酸残基积累导致构象受到限制，使蛋白质的柔韧性降低。另一方面，SHORT VEGETATIVE PHASE（非枢纽）由于 C 末端结构域插入而能够获得蛋白质-蛋白质相互作用，从而允许更大的相互作用界面。这些发现表明，当结合机制涉及诱导契合或构象选择时，蛋白质相互作用的进化发生在构象动力学的水平上。当蛋白质相互作用网络的复杂性需要特异性时，蛋白质可以在降低灵活性的情况下进化为更高的特异性。
