Crystal structure of the 2′-specific and double-stranded RNA-activated interferon-induced antiviral protein 2′-5′-oligoadenylate synthetase
Crystal structure of the 2′-specific and double-stranded RNA-activated interferon-induced antiviral protein 2′-5′-oligoadenylate synthetase
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DOI：
10.1016/s1097-2765(03)00433-7
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发表时间：
2003-11-01
期刊：
影响因子：
16
通讯作者：
Yee, VC
中科院分区：
文献类型：
--
作者：
Hartmann, R;Justesen, J;Yee, VC
2 '-5'-寡腺苷酸合成酶是干扰素诱导的、双链RNA激活的抗病毒酶，其是已知催化2 '-特异性核苷酸转移的唯一蛋白质。这种2 '-5'-寡腺苷酸合成酶的晶体结构揭示了X特异性聚腺苷酸聚合酶的结构保守性，该聚合酶与结构指导的诱变结合，支持2 '-和X特异性核苷酸转移酶的保守催化机制。与其他超家族成员的结构比较表明，供体底物的保守活性位点的功能，而受体底物的非保守区域的方向。2 '-5'-寡聚腺苷酸合成酶被感染细胞中的病毒双链RNA激活，并通过合成2 '-5'-寡聚腺苷酸而引发细胞应答，2 '-5'-寡聚腺苷酸进而激活RNA酶L。这种晶体结构表明，激活涉及结构域-结构域转移，并确定了一个推定的dsRNA激活位点，该位点通过诱变进行探测，从而提供了对病毒双链RNA的细胞识别的结构见解。
2'-5'-oligoadenylate synthetases are interferon-induced, double-stranded RNA-activated antiviral enzymes which are the only proteins known to catalyze 2'-specific nucleotidyl transfer. This crystal structure of a 2'-5'-oligoadenylate synthetase reveals a structural conservation with the X-specific poly(A) polymerase that, coupled with structure-guided mutagenesis, supports a conserved catalytic mechanism for the 2'- and X-specific nucleotidyl transferases. Comparison with structures of other superfamily members indicates that the donor substrates are bound by conserved active site features while the acceptor substrates are oriented by nonconserved regions. The 2'-5'-oligoadenylate synthetases; are activated by viral double-stranded RNA in infected cells and initiate a cellular response by synthesizing 2'-5'-oligoadenylates, which in turn activate RNase L. This crystal structure suggests that activation involves a domain-domain shift and identifies a putative dsRNA activation site that is probed by mutagenesis, thus providing structural insight into cellular recognition of viral double-stranded RNA.