Crystal structure of IRF-3 in complex with CBP
Crystal structure of IRF-3 in complex with CBP
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DOI：
10.1016/j.str.2005.06.011
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发表时间：
2005-09-01
期刊：
影响因子：
5.7
通讯作者：
Lin, K
中科院分区：
文献类型：
--
作者：
Qin, BY;Liu, C;Lin, K
干扰素β（IFN-β）是一种抗病毒细胞因子，其转录激活需要IRF-3和CBP/p300在IFN-β基因的启动子区组装。IRF-3与CBP复合物的晶体结构表明CBP与IRF-3上的疏水表面相互作用，在潜伏的IRF-3中，IRF-3被其自身抑制元件覆盖。这种结构组织表明，病毒诱导的IRF-3的磷酸化激活触发了自抑制元件的解折叠，并暴露了CBP相互作用的相同疏水表面。该结构还揭示了相互作用的CBP片段可以存在于截然不同的构象中，这取决于相关转录辅因子的身份。这一发现表明CBP/p300中可能存在一种调控机制，通过这种机制，相互作用的转录因子可以指定辅激活因子的构象并影响转录结果。
Transcriptional activation of interferon beta (IFN-beta), an antiviral cytokine, requires the assembly of IRF-3 and CBP/p300 at the promoter region of the IFN-beta gene. The crystal structure of IRF-3 in complex with CBP reveals that CBP interacts with a hydrophobic surface on IRF-3, which in latent IRF-3 is covered by its autoinhibitory elements. This structural organization suggests that virus-induced phosphoactivation of IRF-3 triggers unfolding of the autoinhibitory elements and exposes the same hydrophobic surface for CBP interaction. The structure also reveals that the interacting CBP segment can exist in drastically different conformations, depending on the identity of the associating transcription cofactor. The finding suggests a possible regulatory mechanism in CBP/p300, by which the interacting transcription factor can specify the coactivator's conformation and influence the transcriptional outcome.