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标题: 艾滋病治疗新方法：利用人类DNA [打印本页]

作者: ipsvirus 时间: 2015-12-17 17:54
标题: 艾滋病治疗新方法：利用人类DNA

来自萨斯喀彻温大学的科学家们正在尝试用一种新方法来战胜艾滋病病毒（HIV），它是一种基于位于人类基因组的古老“纠错”系统。研究者们希望利用这个防线保护人体免受病毒的攻击。

“纠错”系统指的是一组由七个基因的活动引起的酶，这七个基因分别是APOBEC3-A、B、C、D、F、G 和H。研究发现，当HIV感染人体时，体细胞就会释放这些酶攻击病毒核酸，阻止HIV的增殖。

HIV演化出了一个反应来关闭这些酶，因而自然机制往往无法抑制HIV。

科学家们进一步研究后发现，APOBEC3基因有两个变体：单倍型II和V，它们以不同的方式干扰HIV。因此如果我们使用适当的多肽，来增强这些天然的生物反应，就可以利用这些变体来帮助我们抗击艾滋病。

首席研究员Linda Chelico告诉Laboratory Manager：“这些研究使我们对这几个基因的互作有了一个更好地了解，可以帮助我们在未来更好地治疗艾滋病。”

这项研究发表在The Journal of Biological Chemistry，题为“Natural Polymorphisms and Oligomerization of Human APOBEC3H Contribute to Single-stranded DNA Scanning Ability”。

来源：生物谷

作者: ipsvirus 时间: 2015-12-17 17:55
Natural Polymorphisms and Oligomerization of Human APOBEC3H Contribute to Single-stranded DNA Scanning Ability*

Yuqing Feng, Robin P. Love, Anjuman Ara, Tayyba T. Baig, Madison B. Adolph and Linda Chelico

APOBEC3H is a deoxycytidine deaminase that can restrict the replication of HIV-1 in the absence of the viral protein Vif that induces APOBEC3H degradation in cells. APOBEC3H exists in humans as seven haplotypes (I–VII) with different cellular stabilities. Of the three stable APOBEC3H haplotypes (II, V, and VII), haplotypes II and V occur most frequently in the population. Despite APOBEC3H being a bona fide restriction factor, there has been no comparative biochemical characterization of APOBEC3H haplotypes. We characterized the ssDNA scanning mechanisms that haplotypes II and V use to search their ssDNA substrate for cytosine-containing deamination motifs. APOBEC3H haplotype II was able to processively deaminate multiple cytosines in a single enzyme-substrate encounter by using sliding, jumping, and intersegmental transfer movements. In contrast, APOBEC3H haplotype V exhibited diminished sliding and intersegmental transfer abilities but was able to jump along ssDNA. Due to an Asp or Glu at amino acid 178 differentiating these APOBEC3H haplotypes, the data indicated that this amino acid on helix 6 contributes to processivity. The diminished processivity of APOBEC3H haplotype V did not result in a reduced efficiency to restrict HIV-1 replication in single-cycle infectivity assays, suggesting a redundancy in the contributions of jumping and intersegmental transfer to mutagenic efficiency. Optimal processivity on ssDNA also required dimerization of APOBEC3H through the β2 strands. The findings support a model in which jumping can compensate for deficiencies in intersegmental transfer and suggest that APOBEC3H haplotypes II and V induce HIV-1 mutagenesis efficiently but by different mechanisms.

http://www.jbc.org/content/290/45/27188

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