DNA deamination in immunity: AID in the context of its APOBEC relatives.
DNA deamination in immunity: AID in the context of its APOBEC relatives.
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DOI：
10.1016/s0065-2776(06)94002-4
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发表时间：
2007-01-01
影响因子：
--
通讯作者：
Neuberger, Michael S
中科院分区：
文献类型：
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作者：
Conticello, Silvestro G;Langlois, Marc-Andre;Neuberger, Michael S
激活诱导胞苷脱氨酶 (AID)/载脂蛋白 B RNA 编辑催化成分 (APOBEC) 家族是锌 (Zn) 依赖性脱氨酶超家族的脊椎动物限制亚群，其成员分布在整个生物界。 AID 和 APOBEC2 是最古老的家族成员，APOBEC1 和 APOBEC3 后来才出现，仅限于胎盘哺乳动物。许多AID/APOBEC家族成员在多核苷酸上表现出胞苷脱氨酶活性，尽管在不同的生理背景下。在这里，我们在整个 Zn 依赖性脱氨酶超家族的背景下检查 AID/APOBEC 蛋白。在二级结构预测的基础上，我们提出胞嘧啶和 tRNA 脱氨酶可能为 AID/APOBEC 家族提供比胞苷脱氨酶更好的结构范式（传统上将它们与胞苷脱氨酶进行比较）。这些比较产生了关于 AID/APOBEC3 中可能的多核苷酸相互作用残基的预测，这些预测得到了诱变研究的支持。我们还重点关注 AID 和 APOBEC3 之间的具体比较。两者都是在免疫中发挥作用的 DNA 脱氨酶，并负责其靶底物的超突变。 AID 在适应性免疫系统中发挥作用，使抗体多样化，而靶向 DNA 脱氨是该功能的核心。 APOBEC3 是逆转录病毒先天免疫途径的一部分，靶向 DNA 脱氨是其逆转录病毒超突变活性的核心。然而，APOBEC3 实现逆转录病毒限制功能的机制仍未解决。
The activation-induced cytidine deaminase (AID)/apolipoprotein B RNA-editing catalytic component (APOBEC) family is a vertebrate-restricted subgrouping of a superfamily of zinc (Zn)-dependent deaminases that has members distributed throughout the biological world. AID and APOBEC2 are the oldest family members with APOBEC1 and the APOBEC3s being later arrivals restricted to placental mammals. Many AID/APOBEC family members exhibit cytidine deaminase activity on polynucleotides, although in different physiological contexts. Here, we examine the AID/APOBEC proteins in the context of the entire Zn-dependent deaminase superfamily. On the basis of secondary structure predictions, we propose that the cytosine and tRNA deaminases are likely to provide better structural paradigms for the AID/APOBEC family than do the cytidine deaminases, to which they have conventionally been compared. These comparisons yield predictions concerning likely polynucleotide-interacting residues in AID/APOBEC3s, predictions that are supported by mutagenesis studies. We also focus on a specific comparison between AID and the APOBEC3s. Both are DNA deaminases that function in immunity and are responsible for the hypermutation of their target substrates. AID functions in the adaptive immune system to diversify antibodies with targeted DNA deamination being central to this function. APOBEC3s function as part of an innate pathway of immunity to retroviruses with targeted DNA deamination being central to their activity in retroviral hypermutation. However, the mechanism by which the APOBEC3s fulfill their function of retroviral restriction remains unresolved.