Dramićanin Marija, Ramón-Maiques Santiago
Structural Bases of Genome Integrity Group; Structural Biology and Biocomputing Programme; Spanish National Cancer Research Centre (CNIO); Madrid, Spain.
Mob Genet Elements. 2013 Sep 1;3(5):e27515. doi: 10.4161/mge.27515. Epub 2013 Dec 12.
Transposition target immunity is a phenomenon observed in some DNA transposons that are able to distinguish the host chromosome from their own DNA sequence, thus avoiding self-destructive insertions. The first molecular insight into target selection and immunity mechanisms came from the study of phage Mu transposition, which uses the protein MuB as a barrier to self-insertion. MuB is an ATP-dependent non-specific DNA binding protein that regulates the activity of the MuA transposase and captures target DNA for transposition. However, a detailed mechanistic understanding of MuB functioning was hindered by the poor solubility of the MuB-ATP complexes. Here we comment on the recent discovery that MuB is an AAA+ ATPase that upon ATP binding assembles into helical filaments that coat the DNA. Remarkably, the helical parameters of the MuB filament do not match those of the bound DNA. This intriguing mismatch symmetry led us to propose a model on how MuB targets DNA for transposition, favoring DNA bending and recognition by the transposase at the filament edge. We also speculate on a different protective role of MuB during immunity, where filament stickiness could favor the condensation of the DNA into a compact state that occludes it from the transposase.
转座靶标免疫是在一些DNA转座子中观察到的一种现象，这些转座子能够区分宿主染色体与其自身的DNA序列，从而避免自我毁灭式的插入。对靶标选择和免疫机制的首个分子层面的认识来自于对噬菌体Mu转座的研究，该转座过程利用蛋白质MuB作为自我插入的屏障。MuB是一种依赖ATP的非特异性DNA结合蛋白，它调节MuA转座酶的活性并捕获用于转座的靶标DNA。然而，MuB-ATP复合物的溶解性较差，这阻碍了对MuB功能机制的详细理解。在此，我们对最近的一项发现进行评论，即MuB是一种AAA+ ATP酶，在结合ATP后会组装成覆盖DNA的螺旋丝。值得注意的是，MuB丝的螺旋参数与结合的DNA的螺旋参数不匹配。这种有趣的错配对称性促使我们提出一个关于MuB如何将DNA作为转座靶标的模型，该模型认为MuB有利于DNA弯曲，并促进转座酶在丝边缘对DNA的识别。我们还推测了MuB在免疫过程中的另一种保护作用，即丝的粘性可能有利于DNA凝聚成紧密状态，从而使转座酶无法接触到它。
