Specific DNA recognition mediated by a type IV pilin
Specific DNA recognition mediated by a type IV pilin
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DOI：
10.1073/pnas.1218832110
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发表时间：
2013-02-19
影响因子：
11.1
通讯作者：
Pelicic, Vladimir
中科院分区：
文献类型：
--
作者：
Cehovin, Ana;Simpson, Peter J.;Pelicic, Vladimir
自然转化是细菌进化的主导力量，它通过促进基因水平转移而发挥作用。这一过程可能会产生毁灭性的后果，如抗生素耐药性的传播或高毒性克隆的出现。然而，外源DNA的吸收和重组通常对感受态物种有害。因此，包括人类病原体脑膜炎奈瑟氏球菌（Neisseria meningitidis）在内的模型天然可转化革兰氏阴性细菌已经进化出优先摄取含有短且属特异性序列基序的同型DNA的手段。尽管几十年的深入研究，奈瑟菌属物种的DNA摄取序列受体仍然难以捉摸。在这里，我们表明，使用多学科的方法相结合的生物化学，分子遗传学和结构生物学，脑膜炎球菌IV型皮利结合DNA通过未成年人菌毛蛋白ComP通过一个正电性条纹，预计将暴露在细丝表面和ComP显示一个精致的结合偏好的DNA摄取序列。我们的研究结果阐明了自然转化的最早阶段，揭示了DNA结合的非常规机制，并表明选择性DNA摄取比以前认为的更普遍。
Natural transformation is a dominant force in bacterial evolution by promoting horizontal gene transfer. This process may have devastating consequences, such as the spread of antibiotic resistance or the emergence of highly virulent clones. However, uptake and recombination of foreign DNA are most often deleterious to competent species. Therefore, model naturally transformable Gram-negative bacteria, including the human pathogen Neisseria meningitidis, have evolved means to preferentially take up homotypic DNA containing short and genus-specific sequence motifs. Despite decades of intense investigations, the DNA uptake sequence receptor in Neisseria species has remained elusive. We show here, using a multidisciplinary approach combining biochemistry, molecular genetics, and structural biology, that meningococcal type IV pili bind DNA through the minor pilin ComP via an electropositive stripe that is predicted to be exposed on the filaments surface and that ComP displays an exquisite binding preference for DNA uptake sequence. Our findings illuminate the earliest step in natural transformation, reveal an unconventional mechanism for DNA binding, and suggest that selective DNA uptake is more widespread than previously thought.