摘要
与APOBEC3s其他成员相比,APOBEC3C是特殊的,因为APOBEC3C的抗病毒和抗逆转录元件的功能较弱。APOBEC3C只有一个与锌离子协调的胞嘧啶脱氨酶域,并根据氨基酸特异性被划分为A3Z2。与APOBEC3G相比,APOBEC3C引发HIV-1DNA上胞嘧啶脱氨基的数目较少,所以降低了其抑制HIV-1逆转录及整合的能力。APOBEC3C可在靶细胞引起G→A突变,而G→A突变能导致病毒多样性却无法抑制病毒复制。人类APOBEC3C编码的S188I多态性增强了蛋白质的酶促活性及其抑制HIV-1的能力。另外,人类APOEC3C酶的二聚化增加了单链DNA的持续合成能力,可导致体外和细胞内逆转录过程中的大量突变。APOBEC3C已在灵长类的正选择下进化,是病毒在天然感染过程中必须对抗的重要屏障。因此,对APOBEC3C的研究可为抗病毒和抗癌症的治疗设计提供一些思路。
APOBEC3 C is special as it has only weak antiviral functions and weakly restricts retroelements compared to other APOBEC3 s. APOBEC3 has only one cytidine deaminase domain which coordinates a zinc ion,and then is classified to A3 Z2 according to the amino acid specificity. APOBEC3 C induces less cytidine deamination in HIV-1 DNA than APOBEC3 G and has reduced ability to inhibit HIV-1 reverse transcription and integration compared to APOBEC3 G. APOBEC3 C induces G-to-A mutation that cannot block viral replications but contribute more to viral diversity. A single nucleotide polymorphism in human APOBEC3 C,a change from serine to isoleucine at position 188,results in increased enzymatic activity and potent antiviral activity against HIV-1. Dimerization of human APOBEC3 C increases the ability of continuous synthesis of single-stranded DNA,resulting in higher levels of mutation during reverse transcription in vitro and in cells. APOBEC3 C has evolved under positive selection in primates,and it is an important barrier that must be countered by the virus during natural infections. Therefore,research on APOBEC3 C may provide some ideas for anti-retroviral and anti-cancer therapeutic design.
引文
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