Common semiopen conformations of Mg2+-free Ras, Rho, Rab, Arf, and Ran proteins combined with GDP and their similarity with GEF-bound forms.
Common semiopen conformations of Mg2+-free Ras, Rho, Rab, Arf, and Ran proteins combined with GDP and their similarity with GEF-bound forms.
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DOI：
10.1021/ja0467972
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发表时间：
2005-10
影响因子：
15
通讯作者：
K. Mori;M. Hata;S. Neya;T. Hoshino
中科院分区：
文献类型：
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作者：
K. Mori;M. Hata;S. Neya;T. Hoshino
对小鸟嘌呤核苷酸结合蛋白（GNBPs）Ras、Rho、Rab、Arf和Ran与GDP复合后的无Mg（2+）构象进行了计算研究。采用分子动力学（MD）方法模拟了Mg（2+）离子对GNBPs结构的影响。结果表明，所有无Mg（2+）的GNBP在开关区和核苷酸结合位点之间形成了一个凹槽。在一些GNBP家族中，Mg（2+）的释放被报道在结合鸟嘌呤核苷酸交换因子（GEF）促进GDP/GTP交换反应中起重要作用。有趣的是，在MD模拟中出现的凹槽与在GNBP-GEF复合物中实验观察到的凹槽相似。我们还计算了Mg（2+）-结合的GNBP与Mg（2+）-游离形式进行比较。在Mg（2+）结合的GNBP中没有观察到沟槽。这些结果表明，Mg（2+）离子的调节作用，准备一个模板的GEF结合。结果表明，Mg 2+离子的释放导致GEF-GNBP的结合。
A computational study was performed on the Mg(2+)-free conformations of the small guanine nucleotide-binding proteins (GNBPs): Ras, Rho, Rab, Arf, and Ran, which were complexed with GDP. Molecular dynamics (MD) simulation was executed for each complex for the duration of 3.0 ns to investigate the effects of Mg(2+) ions on the GNBPs' structure. The results indicated that all Mg(2+)-free GNBPs formed a groove between the switch region and the nucleotide-binding site. In some GNBP families, the release of Mg(2+) was reported to play an important role in binding the guanine nucleotide-exchanging factor (GEF) promoting the GDP/GTP exchange reaction. Interestingly, the grooves, which appeared in the MD simulations, were similar to the grooves experimentally observed in the GNBP-GEF complex. We also calculated the Mg(2+)-bound GNBPs to compare with the Mg(2+)-free forms. No groove was observed in the Mg(2+)-bound GNBPs. These results demonstrated a regulatory role of Mg(2+) ion to prepare a template for the GEF binding. Moreover, the results suggested that the release of Mg(2+) ion lead to the GEF-GNBP binding.