抗病毒APOBEC3G催化域的晶体结构和功能影响
Lauren G Holden1, Courtney Prochnow, Y Paul Chang
1Molecular and Computational Biology, University of Southern California, Los Angeles, California 90089, USA.
Nature
|October 14, 2008
概括
该研究揭示了APOBEC3G-CD2的高分辨率晶体结构,APOBEC3G-CD2是一种限制病毒复制的蛋白质. 这种结构澄清了活性部位,并确定了APOBEC家族中基质特异性和DNA结合的关键残留物.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- APOBEC家族蛋白质在各种生物过程中起着至关重要的作用.
- 已知APOBEC3G (A3G) 通过cytidine去胺和RNA结合来限制HIV和HBV等病毒的复制.
研究的目的:
- 为了确定APOBEC3G (APOBEC3G-CD2) 的碳氧终端除氨酶域的高分辨率晶体结构.
- 阐明APOBEC3G的脱氨酶活性和基质特异性的结构基础.
主要方法:
- 净化APOBEC3G-CD2从大肠杆菌.
- 高分辨率的X射线晶体学以确定蛋白质结构.
- 局部定向的突变发生,以调查残留物的功能.
主要成果:
- APOBEC3G-CD2的晶体结构显示了一个保存的五链β-sheet核心,类似于其他deaminases.
- 鉴定出由活点环形成的独特的"基底",其方向与之前的NMR预测有所不同.
- 突变分析确定了对基质特异性,单链DNA结合和除氨酶活性至关重要的关键残留物.
结论:
- 确定的结构为APOBEC3G除氨酶机制提供了关键的见解.
- 了解基质槽和关键残留物为破译APOBEC家族基质特异性奠定了基础.
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