HIV-1 integrase crosslinked oligomers are active in vitro.
HIV-1 integrase crosslinked oligomers are active in vitro.
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DOI：
10.1093/nar/gki241
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发表时间：
2005
影响因子：
14.9
通讯作者：
Parissi V
中科院分区：
文献类型：
--
作者：
Faure A;Calmels C;Desjobert C;Castroviejo M;Caumont-Sarcos A;Tarrago-Litvak L;Litvak S;Parissi V
活性人类免疫缺陷病毒1型（HIV-1）整合酶（IN）的寡聚状态尚未得到明确阐明。我们分析了通过铂交联稳定化后获得的重组IN的不同纯化寡聚形式的活性。通过凝胶色谱分离的交联四聚体能够在体外催化两个病毒LTR末端到靶DNA中的全位点整合，而分离的二聚体形式的酶仅参与一个病毒末端的加工和整合。通过克隆和测序证实了IN四聚体的精确协同整合。DNA整合酶复合物的动力学研究使我们提出了一个模型来解释活性复合物的形成。我们的数据表明，结合到病毒DNA末端的四聚体IN是参与两个LTR协同整合的最小复合物，并且应该是未来抑制剂靶向的寡聚体形式。
The oligomeric state of active human immunodeficiency virus type 1 (HIV-1) integrase (IN) has not been clearly elucidated. We analyzed the activity of the different purified oligomeric forms of recombinant IN obtained after stabilization by platinum crosslinking. The crosslinked tetramer isolated by gel chromatography was able to catalyze the full-site integration of the two viral LTR ends into a target DNA in vitro, whereas the isolated dimeric form of the enzyme was involved in the processing and integration of only one viral end. Accurate concerted integration by IN tetramers was confirmed by cloning and sequencing. Kinetic studies of DNA-integrase complexes led us to propose a model explaining the formation of an active complex. Our data suggest that the tetrameric IN bound to the viral DNA ends is the minimal complex involved in the concerted integration of both LTRs and should be the oligomeric form targeted by future inhibitors.
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