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Abstract：
The Drosophila downstream receptor kinase (Drk), a homologue of human GRB2, participates in the signal transduction from the extracellular to the intracellular environment. Drk receives signals through the interaction of its Src homology 2 (SH2) domain with the phosphorylated tyrosine residue in the receptor tyrosine kinases (RTKs). Here, we present the solution NMR structure of the SH2 domain of Drk (Drk-SH2), which was determined in the presence of a phosphotyrosine (pY)-containing peptide derived from a receptor tyrosine kinase, Sevenless (Sev). The solution structure of Drk-SH2 possess a common SH2 domain architecture, consisting of three β strands imposed between two α helices. Additionally, we interpret the site-specific interactions of the Drk-SH2 domain with the pY-containing peptide through NMR titration experiments. The dynamics of Drk-SH2 were also analysed through NMR-relaxation experiments as well as the molecular dynamic simulation. The docking simulations of the pY-containing peptide onto the protein surface of Drk-SH2 provided the orientation of the peptide, which showed a good agreement with the analysis of the SH2 domain of GRB2.
摘要：
果蝇下游受体激酶（Drk），人GRB2的同源物,参与从胞外到胞内环境的信号转导。Drk通过其Src同源性2（SH2）结构域与受体酪氨酸激酶（RTK）中磷酸化的酪氨酸残基的相互作用来接收信号。这里,我们给出了Drk（Drk-SH2）的SH2域的溶液NMR结构，这是在存在来自受体酪氨酸激酶的含磷酸酪氨酸（pY）的肽的情况下确定的，七（Sev）。Drk-SH2的解决方案结构具有通用的SH2域体系结构，由施加在两个α螺旋之间的三条β链组成。此外,我们通过NMR滴定实验解释了Drk-SH2结构域与含pY肽的位点特异性相互作用.还通过NMR弛豫实验和分子动力学模拟分析了Drk-SH2的动力学。含有pY的肽在Drk-SH2的蛋白质表面上的对接模拟提供了肽的方向，与GRB2的SH2域分析结果吻合良好。
