The crystal structure of the IκBα/NF-κB complex reveals mechanisms of NF-κB inactivation
The crystal structure of the IκBα/NF-κB complex reveals mechanisms of NF-κB inactivation
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DOI：
10.1016/s0092-8674(00)81699-2
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发表时间：
1998-12-11
期刊：
影响因子：
64.5
通讯作者：
Ghosh, G
中科院分区：
文献类型：
--
作者：
Huxford, T;Huang, DB;Ghosh, G
I κ B α通过形成稳定的I κ B α/NF-κ B复合物调节转录因子NF-κ B。在诱导之前，I κ B α将NF-κ B保留在细胞质中，直到接收到NF-κ B激活信号。活化后，NF-κ B通过与核I κ B α结合而从基因启动子中去除，恢复诱导前状态。I κ B α与NF-κ B p50/p65异二聚体复合的2.3埃晶体结构揭示了这些抑制活性的机制。I κ B α的存在允许NF-κ B p65亚基氨基末端结构域的大的整体移动。这种构象变化诱导NF-κ B DNA结合的变构抑制。紧邻NF-κ B p50和p65亚基核定位信号之前的氨基酸残基与I kappa B α氨基末端锚蛋白重复序列相连，阻碍NF-κ B的核输入机制识别。
I kappa B alpha regulates the transcription factor NF-kappa B through the formation of stable I kappa B alpha/NF-kappa B complexes. Prior to induction, I kappa B alpha retains NF-kappa B in the cytoplasm until the NF-kappa B activation signal is received. After activation, NF-kappa B is removed from gene promoters through association with nuclear I kappa B alpha, restoring the preinduction state. The 2.3 Angstrom crystal structure of I kappa B alpha in complex with the NF-kappa B p50/p65 heterodimer reveals mechanisms of these inhibitory activities. The presence of I kappa B alpha allows large en bloc movement of the NF-kappa B p65 subunit amino-terminal domain. This conformational change induces allosteric inhibition of NF-kappa B DNA binding. Amino acid residues immediately preceding the nuclear localization signals of both NF-kappa B p50 and p65 subunits are tethered to the I kappa B alpha aminoterminal ankyrin repeats, impeding NF-kappa B from nuclear import machinery recognition.