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A structural basis for allosteric control of DNA recombination by lambda integrase

机译：Lambda整合酶对DNA重组进行变构控制的结构基础

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摘要

Site-specific DNA recombination is important for basic cellular functions including viral integration, control of gene expression, production of genetic diversity and segregation of newly replicated chromosomes, and is used by bacteriophage lambda to integrate or excise its genome into and out of the host chromosome. lambda recombination is carried out by the bacteriophage-encoded integrase protein (lambda-int) together with accessory DNA sites and associated bending proteins that allow regulation in response to cell physiology. Here we report the crystal structures of lambda-int in higher-order complexes with substrates and regulatory DNAs representing different intermediates along the reaction pathway. The structures show how the simultaneous binding of two separate domains of lambda-int to DNA facilitates synapsis and can specify the order of DNA strand cleavage and exchange. An intertwined layer of amino-terminal domains bound to accessory (arm) DNAs shapes the recombination complex in a way that suggests how arm binding shifts the reaction equilibrium in favour of recombinant products.
机译：特定于位点的DNA重组对于基本的细胞功能非常重要，包括病毒整合，基因表达控制，遗传多样性的产生和新复制染色体的分离，并且噬菌体λ可将其用于整合或切除其基因组进出宿主染色体。 Lambda重组是通过噬菌体编码的整合酶蛋白（lambda-int）与辅助DNA位点和相关的弯曲蛋白进行的，这些蛋白允许响应细胞生理而进行调节。在这里，我们报告了lambda-int晶体结构的高阶复合物，其底物和调控DNA代表了沿着反应途径的不同中间体。该结构显示了lambda-int的两个单独结构域与DNA的同时结合如何促进突触，并可以指定DNA链切割和交换的顺序。结合至辅助（臂）DNA的氨基末端结构域的缠结层以重组方式形成重组复合物，暗示了臂结合如何改变反应平衡而有利于重组产物。

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