一种特异性单克隆抗体的Fab片段对人免疫缺陷病毒1型整合酶的抑制作用表明，不同的酶促功能需要不同的多聚化状态。
Inhibition of human immunodeficiency virus type 1 integrase by the Fab fragment of a specific monoclonal antibody suggests that different multimerization states are required for different enzymatic functions.
作者信息
Barsov E V, Huber W E, Marcotrigiano J, Clark P K, Clark A D, Arnold E, Hughes S H
机构信息
ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA.
出版信息
J Virol. 1996 Jul;70(7):4484-94. doi: 10.1128/JVI.70.7.4484-4494.1996.
Abstract
We have characterized a murine monoclonal antibody (MAb 35), which was raised against human immunodeficiency virus type 1 (HIV-1) integration protein (IN), and the corresponding Fab 35. Although MAb 35 does not inhibit HIV-1 IN, Fab 35 does. MAb 35 (and Fab 35) binds to an epitope in the C-terminal region of HIV-1 IN. Fab 35 inhibits 3'-end processing, strand transfer, and disintegration; however, DNA binding is not affected. The available data suggest that Fab 35 inhibits enzymatic activities of IN by interfering with the ability of IN to form multimers that are enzymatically active. This implies that the C-terminal region of HIV-1 IN participates in interactions that are essential for the multimerization of IN. Titration of the various IN-mediated enzymatic activities suggests that different degrees of multimerization are required for different activities of HIV-1 IN.
摘要
我们已对一种鼠源单克隆抗体（单克隆抗体35）及其相应的Fab 35进行了特性鉴定，该单克隆抗体是针对1型人类免疫缺陷病毒（HIV-1）整合蛋白（IN）产生的。尽管单克隆抗体35不抑制HIV-1 IN，但Fab 35可以。单克隆抗体35（和Fab 35）与HIV-1 IN C末端区域的一个表位结合。Fab 35抑制3'末端加工、链转移和解离；然而，DNA结合不受影响。现有数据表明，Fab 35通过干扰IN形成具有酶活性的多聚体的能力来抑制IN的酶活性。这意味着HIV-1 IN的C末端区域参与了对IN多聚化至关重要的相互作用。对各种IN介导的酶活性进行滴定表明，HIV-1 IN的不同活性需要不同程度的多聚化。
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