Observation by Real-Time NMR and Interpretation of Length- and Location-Dependent Deamination Activity of APOBEC3B,ACS Chemical Biology

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Observation by Real-Time NMR and Interpretation of Length- and Location-Dependent Deamination Activity of APOBEC3B
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2017-10-03 00:00:00 , DOI: 10.1021/acschembio.7b00662
Li Wan ₁ , Takashi Nagata ₁ , Ryo Morishita ₂ , Akifumi Takaori-Kondo ₃ , Masato Katahira ₁

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Human APOBEC3B (A3B) deaminates a cytosine into a uracil in single-stranded (ss) DNA, resulting in human cancers. A3B’s deamination activity is conferred by its C-terminal domain (CTD). However, little is known about the mechanism by which target sequences are searched and deaminated. Here, we applied a real-time NMR method to elucidate the deamination properties. We found that A3B CTD shows higher activity toward its target sequence in short ssDNA and efficiently deaminates a target sequence located near the center of ssDNA. These properties are quite different from those of well-studied APOBEC3G, which shows higher activity toward its target sequence in long ssDNA and one located close to the 5′-end. The unique properties of the A3B CTD can be rationally interpreted by considering that after nonspecific binding to ssDNA, A3B slides only for a relatively short distance and tends to dissociate from the ssDNA before reaching the target sequence.

中文翻译：

实时NMR观察和解释APOBEC3B的长度和位置相关的脱氨活性

人类APOBEC3B（A3B）将单链（ss）DNA中的胞嘧啶脱氨成尿嘧啶，从而导致人类癌症。A3B的脱氨活性由其C末端结构域（CTD）赋予。但是，关于靶序列被搜索和脱氨的机理知之甚少。在这里，我们应用了实时NMR方法来阐明脱氨性能。我们发现，A3B CTD在短的ssDNA中对其目标序列显示更高的活性，并有效地使位于ssDNA中心附近的目标序列脱氨。这些特性与经过充分研究的APOBEC3G完全不同，APOBEC3G在长ssDNA中显示出对其靶序列的更高活性，并且靠近5'端。考虑到在与ssDNA非特异性结合后，A3B CTD的独特性质可以得到合理的解释。

更新日期：2017-10-03

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