Structural insights into the intertwined dimer of fyn SH2
Structural insights into the intertwined dimer of fyn SH2
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DOI：
10.1002/pro.2806
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发表时间：
2015-12-01
期刊：
影响因子：
8
通讯作者：
van Nuland, Nico
中科院分区：
文献类型：
--
作者：
Huculeci, Radu;Garcia-Pino, Abel;van Nuland, Nico
Src同源结构域是相互作用模块，专门用于识别细胞内信号通路中许多蛋白质中结合的磷酸酪氨酸位点。本研究首次提供了Fyn SH2在溶液和晶体条件下二聚化的结构洞察，提供了Fyn SH2二聚体和肽结合结构的新晶体结构。利用核磁共振化学位移分析，我们展示了肽如何能够消除二聚化，导致单分子SH2在其结合状态。此外，我们发现Fyn SH2的二聚体形式不同于之前报道的其他SH2二聚体。有趣的是，Fyn二聚体可以用来构建一个完整的Fyn二聚体模型，没有任何空间冲突。总之，这些结果扩展了我们对SH2二聚化的理解，一方面给出了结构细节，另一方面提出了这种行为可能的生理相关性。
Src homology 2 domains are interaction modules dedicated to the recognition of phosphotyrosine sites incorporated in numerous proteins found in intracellular signaling pathways. Here we provide for the first time structural insight into the dimerization of Fyn SH2 both in solution and in crystalline conditions, providing novel crystal structures of both the dimer and peptidebound structures of Fyn SH2. Using nuclear magnetic resonance chemical shift analysis, we show how the peptide is able to eradicate the dimerization, leading to monomeric SH2 in its bound state. Furthermore, we show that Fyn SH2's dimer form differs from other SH2 dimers reported earlier. Interestingly, the Fyn dimer can be used to construct a completed dimer model of Fyn without any steric clashes. Together these results extend our understanding of SH2 dimerization, giving structural details, on one hand, and suggesting a possible physiological relevance of such behavior, on the other hand.