APOBEC-2晶体结构和对除氨酶的功能影响 AID
Courtney Prochnow1, Ronda Bransteitter, Michael G Klein
1Molecular and Computational Biology, University of Southern California Los Angeles, California 90089, USA.
Nature
|December 26, 2006
概括
阿波利波蛋白B信使RNA编辑酶催化聚二 (APOBEC-2) 的晶体结构显示出一种独特的棒状四聚. 这种结构提供了有关蛋白质的突变,如激活诱导的cytidine deaminase,如何影响抗体成熟的见解.
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-2 (APO2) 是APOBEC家族的一部分,以消除mRNA和单链DNA的氨基酸而闻名.
- APOBEC 蛋白质执行各种生物功能,包括产生抗体 (AID) 和抗病毒防御 (APOBEC-3).
研究的目的:
- 为了确定APOBEC-2 (APO2) 的晶体结构.
- 了解APO2的四重体形成的结构基础及其对APOBEC家族功能的影响.
主要方法:
- 进行X射线晶体学以确定APO2的结构.
- 基于结构的预测被测试在激活诱导的cytidine deaminase (AID) 上,由于序列同质性.
主要成果:
- APO2形成了一个独特的棒状四聚体,与cytidine deaminase的方形四聚体不同.
- 具有两个长的α螺旋体的APO2单体结构,促进了头对头二极体相互作用,形成棒形四极体.
- 从APO2结构中预测的影响AID的寡合化和基质访问的突变,损害了其去胺活性.
结论:
- APO2结构揭示了APOBEC家族中的一个新的四度组合机制.
- 了解APO2的结构为解释AID突变如何导致超IgM-2综合征和抗体成熟缺陷提供了一个框架.
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