Structural basis for the regulatory function of a complex zinc-binding domain in a replicative arterivirus helicase resembling a nonsense-mediated mRNA decay helicase.
Structural basis for the regulatory function of a complex zinc-binding domain in a replicative arterivirus helicase resembling a nonsense-mediated mRNA decay helicase.
复制标题
复制动脉病毒解旋酶中复杂锌结合域调节功能的结构基础，类似于无义介导的mRNA衰变解旋酶
DOI：
10.1093/nar/gkt1310
复制
发表时间：
2014-03
影响因子：
14.9
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Deng Z;Lehmann KC;Li X;Feng C;Wang G;Zhang Q;Qi X;Yu L;Zhang X;Feng W;Wu W;Gong P;Tao Y;Posthuma CC;Snijder EJ;Gorbalenya AE;Chen Z
所有具有基因组>；∼7kb的正链核糖核酸病毒都编码螺旋酶，而螺旋酶的特性通常很差。NIDV超家族1解旋酶(HEL1)的核心与一个独特的N-末端锌结合结构域(ZBD)相关，该结构域以前参与解旋酶的调节、基因组复制和亚基因组mRNA的合成。动脉病毒解旋酶(NSP10)的高分辨率结构，单独和与多核苷酸底物的复合体，现在提供了对NidVirus解旋酶功能的结构基础的第一次洞察。一个先前未知的结构域1B将HEL1结构域1A和2A连接到ZBD的长连接子，ZBD的长连接子进一步由一个新的环状模块和三个三叉锌指组成，共同配位三个锌原子。在底物结合方面，HEL1结构域之外的主要构象变化明显，尤其是在结构域1B。结构表征、诱变和生化分析表明，解旋酶的活性依赖于ZBD和HEL1结构域之间广泛的相互作用。动脉病毒解旋酶在结构上类似于细胞内的UPF1解旋酶，这表明NidoVirus也可能利用其解旋酶对其大的RNA基因组进行转录后质量控制。
All positive-stranded RNA viruses with genomes >∼7 kb encode helicases, which generally are poorly characterized. The core of the nidovirus superfamily 1 helicase (HEL1) is associated with a unique N-terminal zinc-binding domain (ZBD) that was previously implicated in helicase regulation, genome replication and subgenomic mRNA synthesis. The high-resolution structure of the arterivirus helicase (nsp10), alone and in complex with a polynucleotide substrate, now provides first insights into the structural basis for nidovirus helicase function. A previously uncharacterized domain 1B connects HEL1 domains 1A and 2A to a long linker of ZBD, which further consists of a novel RING-like module and treble-clef zinc finger, together coordinating three Zn atoms. On substrate binding, major conformational changes were evident outside the HEL1 domains, notably in domain 1B. Structural characterization, mutagenesis and biochemistry revealed that helicase activity depends on the extensive relay of interactions between the ZBD and HEL1 domains. The arterivirus helicase structurally resembles the cellular Upf1 helicase, suggesting that nidoviruses may also use their helicases for post-transcriptional quality control of their large RNA genomes.
登录
查看更多内容
影响因子：
14.9
作者：
Gorbalenya AE;Koonin EV;Donchenko AP;Blinov VM
通讯作者：
Blinov VM
SARS冠状病毒的化学抑制剂的开发：病毒解旋酶是潜在靶标。
影响因子：
5.8
作者：
Keum YS;Jeong YJ
通讯作者：
Jeong YJ
影响因子：
5
作者：
Gorbalenya AE;Enjuanes L;Ziebuhr J;Snijder EJ
通讯作者：
Snijder EJ
影响因子：
6.8
作者：
GORBALENYA, AE;KOONIN, EV
通讯作者：
KOONIN, EV
DOI：
10.1016/b978-0-12-384684-6.00066-5
发表时间：
2011-11-23
期刊：
Virus Taxonomy
影响因子：
--
作者：
通讯作者：
--