Crystal structure of IRF-3 reveals mechanism of autoinhibition and virus-induced phosphoactivation
Crystal structure of IRF-3 reveals mechanism of autoinhibition and virus-induced phosphoactivation
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DOI：
10.1038/nsb1002
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发表时间：
2003-11-01
期刊：
影响因子：
--
通讯作者：
Lin, K
中科院分区：
文献类型：
--
作者：
Qin, BY;Liu, C;Lin, K
IRF-3是转录因子干扰素调节因子（IRF）家族的成员，作为抗病毒活性的分子开关发挥作用。IRF-3利用自身抑制机制来抑制其在未感染细胞中的反式激活潜力，并且病毒感染诱导IRF-3的磷酸化和激活以启动抗病毒应答。IRF-3反式激活结构域的晶体结构揭示了独特的自抑制机制，由此IRF缔合结构域和侧翼自抑制元件缩合形成疏水核心。该结构表明，磷酸化重组的自抑制元件，导致一个疏水性的活性位点和重新排列的DNA结合结构域的转录激活的解蔽。IRF-3表现出与Smad蛋白家族的MH 2结构域和FHA结构域显著的结构和表面静电势相似性，这表明在该信号传导介质超家族中存在共同的分子作用机制。
IRF-3, a member of the interferon regulatory factor (IRF) family of transcription factors, functions as a molecular switch for antiviral activity. IRF-3 uses an autoinhibitory mechanism to suppress its transactivation potential in uninfected cells, and virus infection induces phosphorylation and activation of IRF-3 to initiate the antiviral responses. The crystal structure of the IRF-3 transactivation domain reveals a unique autoinhibitory mechanism, whereby the IRF association domain and the flanking autoinhibitory elements condense to form a hydrophobic core. The structure suggests that phosphorylation reorganizes the autoinhibitory elements, leading to unmasking of a hydrophobic active site and realignment of the DNA binding domain for transcriptional activation. IRF-3 exhibits marked structural and surface electrostatic potential similarity to the MH2 domain of the Smad protein family and the FHA domain, suggesting a common molecular mechanism of action among this superfamily of signaling mediators.