Oligomerization transforms human APOBEC3G from an efficient enzyme to a slowly dissociating nucleic acid-binding protein.
Oligomerization transforms human APOBEC3G from an efficient enzyme to a slowly dissociating nucleic acid-binding protein.
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人APOBEC 3蛋白是一个DNA编辑酶家族，在先天免疫应答中发挥重要作用，并对逆转录病毒和逆转录转座子具有广泛的活性。APOBEC 3G是该家族的成员，在缺乏病毒感染因子Vif的情况下抑制HIV-1复制。HIV复制的抑制通过病毒单链DNA的脱氨基和脱氨基独立机制发生。有效的脱氨需要与ssDNA快速结合和解离。然而，一个相对缓慢的解离速率是必需的脱氨酶独立的路障机制，其中APOBEC 3G结合病毒模板链和阻断逆转录酶催化的DNA延伸。在这里，我们表明，APOBEC 3G最初结合ssDNA与快速的开关速率，随后转化为一个缓慢的解离模式。相比之下，寡聚化缺陷型APOBEC 3G突变体没有表现出缓慢的解离速率。我们提出催化活性单体或二聚体在病毒基因组上缓慢寡聚并抑制逆转录。
The human APOBEC3 proteins are a family of DNA-editing enzymes that play an important role in the innate immune response and have broad activity against retroviruses and retrotransposons. APOBEC3G is a member of this family that inhibits HIV-1 replication in the absence of the viral infectivity factor Vif. Inhibition of HIV replication occurs by both deamination of viral single-stranded DNA and a deamination-independent mechanism. Efficient deamination requires rapid binding to and dissociation from ssDNA. However, a relatively slow dissociation rate is required for the proposed deaminase-independent roadblock mechanism in which APOBEC3G binds the viral template strand and blocks reverse transcriptase-catalyzed DNA elongation. Here we show that APOBEC3G initially binds ssDNA with rapid on-off rates and subsequently converts to a slowly dissociating mode. In contrast, an oligomerization-deficient APOBEC3G mutant did not exhibit a slow off rate. We propose that catalytically active monomers or dimers slowly oligomerize on the viral genome and inhibit reverse transcription.
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影响因子：
11.7
作者：
Chaurasiya, Kathy R.;Paramanathan, Thayaparan;McCauley, Micah J.;Williams, Mark C.
通讯作者：
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影响因子：
64.5
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Harris, RS;Bishop, KN;Malim, MH
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APOBEC3G对RNA的结合控制逆转录病毒的脱氨基依赖性限制。
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56.9
作者：
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4.1
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