The μ transpososome structure sheds light on DDE recombinase evolution.
The μ transpososome structure sheds light on DDE recombinase evolution.
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噬菌体Mu转座的研究为理解逆转录病毒整合和V（D）J重组以及许多其他DNA转座反应铺平了道路。在这里，我们报告的Mu转座酶（MuA）的结构与噬菌体DNA末端和靶DNA的复合物，确定从数据，各向异性扩展到5.2/5.2/3.7 μ m的分辨率，结合先前确定的结构的个别域。这种高度交织的结构说明了为什么化学活性取决于突触复合物的形成，并揭示了单个结构域在与不同位点结合时发挥不同的作用。它还建议解释增加的稳定性的最终产品复合物和其优先识别的ATP依赖性解折叠酶ClpX。虽然MuA和许多其他重组酶共享一个结构保守的“DDE”催化结构域，但有限的可用复杂结构之间的比较表明，一些保守的特征，如反式催化和靶DNA弯曲，是通过趋同进化产生的，因为它们对功能很重要。
Studies of bacteriophage Mu transposition paved the way for understanding retroviral integration and V(D)J recombination as well as many other DNA transposition reactions. Here we report the structure of Mu transposase (MuA) in complex with bacteriophage DNA ends and target DNA, determined from data that extend anisotropically to 5.2/5.2/3.7Å resolution, in conjunction with previously-determined structures of individual domains. The highly intertwined structure illustrates why chemical activity depends on formation of the synaptic complex, and reveals that individual domains play different roles when bound to different sites. It also suggests explanations for the increased stability of the final product complex and for its preferential recognition by the ATP-dependent unfoldase ClpX. Although MuA and many other recombinases share a structurally conserved “DDE” catalytic domain, comparisons among the limited set of available complex structures suggest that some conserved features, such as catalysis in trans and target DNA bending, arose through convergent evolution because they are important for function.