APOBEC3C的研究进展

Research on APOBEC3C

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。

APOBEC3C is special as it has only weak antiviral functions and weakly restricts retroelements compared to other APOBEC3s.APOBEC3 has only one cytidine deaminase domain which coordinates a zinc ion,and then is classified to A3Z2 according to the amino acid specificity.APOBEC3C induces less cytidine deamination in HIV-1 DNA than APOBEC3G and has reduced ability to inhibit HIV-1 reverse transcription and integration compared to APOBEC3G.APOBEC3C induces G-to-A mutation that cannot block viral replications but contribute more to viral diversity.A single nucleotide polymorphism in human APOBEC3C,a change from serine to isoleucine at position 188,results in increased enzymatic activity and potent antiviral activity against HIV-1.Dimerization of human APOBEC3C increases the ability of continuous synthesis of single-stranded DNA,resulting in higher levels of mutation during reverse transcription in vitro and in cells.APOBEC3C 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 APOBEC3C may provide some ideas for anti-retroviral and anti-cancer therapeutic design.