Retroviral DNA integration: reaction pathway and critical intermediates
Retroviral DNA integration: reaction pathway and critical intermediates
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DOI：
10.1038/sj.emboj.7601005
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发表时间：
2006-03-22
期刊：
影响因子：
11.4
通讯作者：
Craigie, R
中科院分区：
文献类型：
--
作者：
Li, M;Mizuuchi, M;Craigie, R
逆转录病毒DNA整合的关键DNA切割和连接步骤由病毒整合酶蛋白进行。整合酶的各个结构域的结构已经确定，但它们在与病毒DNA的活性复合物中的组织是未知的。我们发现，HIV-1整合酶形成稳定的突触复合物，其中整合酶的四聚体与一对病毒DNA末端稳定相关。病毒DNA在这些复合物中被加工，这些复合物继续捕获靶DNA并整合病毒DNA末端。两个病毒DNA末端与靶DNA的连接顺序发生，形成一个稳定的中间复合物，其中只有一个DNA末端连接。整合产物还保持与整合酶稳定结合，并且可能需要在通过细胞酶完成整合过程之前进行分解。结果定义了一系列稳定的核蛋白复合物，介导逆转录病毒DNA整合。
The key DNA cutting and joining steps of retroviral DNA integration are carried out by the viral integrase protein. Structures of the individual domains of integrase have been determined, but their organization in the active complex with viral DNA is unknown. We show that HIV-1 integrase forms stable synaptic complexes in which a tetramer of integrase is stably associated with a pair of viral DNA ends. The viral DNA is processed within these complexes, which go on to capture the target DNA and integrate the viral DNA ends. The joining of the two viral DNA ends to target DNA occurs sequentially, with a stable intermediate complex in which only one DNA end is joined. The integration product also remains stably associated with integrase and likely requires disassembly before completion of the integration process by cellular enzymes. The results define the series of stable nucleoprotein complexes that mediate retroviral DNA integration.