A dynamically tuned double-stranded RNA binding mechanism for the activation of antiviral kinase PKR
A dynamically tuned double-stranded RNA binding mechanism for the activation of antiviral kinase PKR
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DOI：
10.1093/emboj/19.20.5567
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发表时间：
2000-10-16
期刊：
影响因子：
11.4
通讯作者：
Qin, J
中科院分区：
文献类型：
--
作者：
Nanduri, S;Rahman, F;Qin, J
干扰素诱导的抗病毒蛋白激酶PKR激活的关键步骤包括病毒双链RNA(DsRNA)与其两个结构相似的N端dsRNA结合基序dsRBM1和dsRBM2的不同结合，我们在这里利用核磁共振谱显示，与RNA结合活性较低的dsRBM2相比，具有较高RNA结合活性的dsRBM1在毫秒时间尺度上表现出显著的运动灵活性。我们进一步证明，dsRBM2，而不是dsRBM1，与C-末端的激酶域有特异性的相互作用。这些结果表明，PKR激活的dsRNA结合机制是动态调节的，其中运动上更灵活的dsRBM1锚定在dsRNA上，从而诱导dsRBM2与RNA的协同结合，从而暴露激活域。
A key step in the activation of interferon-inducible antiviral kinase PKR involves differential binding of viral double-stranded RNA (dsRNA) to its two structurally similar N-terminal dsRNA binding motifs, dsRBM1 and dsRBM2, We show here, using NMR spectroscopy, that dsRBM1 with higher RNA binding activity exhibits significant motional flexibility on a millisecond timescale as compared with dsRBM2 with lower RNA binding activity. We further show that dsRBM2, but not dsRBM1, specifically interacts with the C-terminal kinase domain. These results suggest a dynamically tuned dsRNA binding mechanism for PKR activation, where motionally more flexible dsRBM1 anchors to dsRNA, thereby inducing a cooperative RNA binding for dsRBM2 to expose the kinase domain.