Huthoff Hendrik, Malim Michael H
Department of Infectious Diseases, Guy's, King's and St Thomas' School of Medicine, King's College London, GKT Guy's Hospital, London SE1 9RT, UK.
Virology. 2005 Apr 10;334(2):147-53. doi: 10.1016/j.virol.2005.01.038.
The human apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G (APOBEC3G, or hA3G) protein, provides cells with an intracellular antiretroviral activity that is associated with the hypermutation of viral DNA through cytidine deamination. Indeed, hA3G belongs to a family of vertebrate proteins that contain one or two copies of a signature sequence motif unique to cytidine deaminases (CTDAs). We have constructed secondary structure models of the APOBEC proteins through a combination of structure prediction and subsequent alignment with nucleotide CTDAs whose structures have been solved to high resolution. Secondary structure elements common to all CTDAs are predicted, in addition to structural features that are apparently unique to the APOBEC family of proteins. Most notably, a putative looped-out helix abuts an amino acid that modulates the susceptibility of A3G proteins to the antagonistic action of the human and simian immunodeficiency virus (HIV and SIV) Vif proteins. Using the structure models as a guide, we reflect on mutagenesis studies of the APOBEC1 (A1), hA3G and activation induced deaminase (AID) proteins, with emphasis on the determinants of cytidine deamination and antiviral activities.
人类载脂蛋白B信使核糖核酸编辑酶催化多肽样3G（APOBEC3G，或hA3G）蛋白为细胞提供了一种细胞内抗逆转录病毒活性，这种活性与通过胞嘧啶脱氨导致病毒DNA的超突变有关。实际上，hA3G属于脊椎动物蛋白家族，该家族包含胞嘧啶脱氨酶（CTDAs）特有的一个或两个拷贝的特征序列基序。我们通过结构预测以及随后与已解析出高分辨率结构的核苷酸CTDAs进行比对，构建了APOBEC蛋白的二级结构模型。除了APOBEC蛋白家族明显独特的结构特征外，还预测了所有CTDAs共有的二级结构元件。最值得注意的是，一个假定的环状螺旋紧邻一个氨基酸，该氨基酸调节A3G蛋白对人类和猿猴免疫缺陷病毒（HIV和SIV）Vif蛋白拮抗作用的敏感性。以这些结构模型为指导，我们思考了对APOBEC1（A1）、hA3G和激活诱导脱氨酶（AID）蛋白的诱变研究，重点关注胞嘧啶脱氨和抗病毒活性的决定因素。
