Molecular Mechanism of RNA Recognition by Zinc-Finger Antiviral Protein
Molecular Mechanism of RNA Recognition by Zinc-Finger Antiviral Protein
复制标题
锌指抗病毒蛋白识别RNA的分子机制
DOI：
10.1016/j.celrep.2019.11.116
复制
发表时间：
2020-01-07
期刊：
影响因子：
8.8
通讯作者：
Gao, Pu
中科院分区：
文献类型：
--
作者：
Luo, Xiu;Wang, Xinlu;Gao, Pu
锌指抗病毒蛋白（ZAP）是一种特异性抑制多种病毒的宿主抗病毒因子。ZAP选择性地与富含CG-二核苷酸的RNA序列结合，并招募多个RNA降解机器来降解靶病毒RNA。然而，ZAP识别特定RNA的分子机制和结构基础尚不清楚。在这里，我们报告的晶体结构的ZAP N-末端结构域结合到一个CG丰富的单链RNA，提供了其特异性识别的CG二核苷酸和额外的鸟嘌呤和胞嘧啶的分子基础。ZAP的四个锌指采用独特的结构并与RNA形成广泛的相互作用。在RNA-ZAP相互作用表面处的蛋白质和RNA两者的突变降低体外结合亲和力和细胞抗病毒活性。这项工作揭示了ZAP识别特定靶RNA的分子机制，也为ZAP协调下游RNA降解过程的机制提供了见解。
Zinc-finger antiviral protein (ZAP) is a host antiviral factor that specifically restricts a wide range of viruses. ZAP selectively binds to CG-dinucleotide-enriched RNA sequences and recruits multiple RNA degradation machines to degrade target viral RNA. However, the molecular mechanism and structural basis for ZAP recognition of specific RNA are not clear. Here, we report the crystal structure of the ZAP N-terminal domain bound to a CG-rich single-stranded RNA, providing the molecular basis for its specific recognition of a CG dinucleotide and additional guanine and cytosine. The four zinc fingers of ZAP adopt a unique architecture and form extensive interactions with RNA. Mutations of both protein and RNA at the RNA-ZAP interacting surface reduce the in vitro binding affinity and cellular antiviral activity. This work reveals the molecular mechanism of ZAP recognition of specific target RNA and also provides insights into the mechanism by which ZAP coordinates downstream RNA degradation processes.