Structure of N-terminal domain of ZAP indicates how a zinc-finger protein recognizes complex RNA
Structure of N-terminal domain of ZAP indicates how a zinc-finger protein recognizes complex RNA
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ZAP N 端结构域的结构表明锌指蛋白如何识别复杂的 RNA
DOI：
10.1038/nsmb.2243
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发表时间：
2012-04-01
影响因子：
16.8
通讯作者：
Liu, Yingfang
中科院分区：
文献类型：
--
作者：
Chen, Shoudeng;Xu, Yihui;Liu, Yingfang
锌指抗病毒蛋白（ZAP）是一种宿主因子，通过靶向降解病毒mRNA来特异性抑制某些病毒（如HIV-1）的复制。ZAP如何识别其靶RNA尚不清楚。在这里，我们报告的晶体结构的N-末端结构域的大鼠ZAP（NZAP 225），主要的功能域。NZAP 225的整体结构类似于拖拉机，底部有四个锌指图案。结构和功能分析确定了多个带正电荷的残基和两个推定的RNA结合腔形成一个大的推定的RNA结合裂缝。ZAP分子相互作用形成二聚体，其结合到含有两个ZAP结合模块的ZAP响应性RNA分子。这些结果为ZAP如何特异性结合复杂的靶RNA提供了见解。
Zinc-finger antiviral protein (ZAP) is a host factor that specifically inhibits the replication of certain viruses, such as HIV-1, by targeting viral mRNA for degradation. How ZAP recognizes its target RNA has been unclear. Here we report the crystal structure of the N-terminal domain of rat ZAP (NZAP225), the major functional domain. The overall structure of NZAP225 resembles a tractor, with four zinc-finger motifs located at the bottom. Structural and functional analyses identified multiple positively charged residues and two putative RNA-binding cavities forming a large putative RNA-binding cleft. ZAP molecules interact to form a dimer that binds to a ZAP-responsive RNA molecule containing two ZAP-binding modules. These results provide insights into how ZAP binds specifically to complex target RNA.