Crystal structure of p50/p65 heterodimer of transcription factor NF-κB bound to DNA
Crystal structure of p50/p65 heterodimer of transcription factor NF-κB bound to DNA
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作者：
Chen, FE;Huang, DB;Ghosh, G
NF-kappa B p50/p65异源二聚体是Rel转录因子家族的经典成员，可调节多种细胞功能，如免疫应答、细胞生长和发育（1-3）。其他哺乳动物Rel家族成员，包括蛋白p52、原癌蛋白c-Rel和RelB，都有氨基末端Rel同源区（rrs）（4-7）。RHR通过与抑制剂kappa B蛋白的复合物形成，负责这些蛋白的二聚化、DNA结合和细胞质定位(8)，信号诱导的kappa B抑制剂的去除允许二聚体转位到细胞核，并对含有kappa B DNA的基因进行转录调节(9)，NF-kappa B特异性识别kappa B DNA元件（1,10,11），其一致序列为5'- gggrnyyyc -3' (R是未指定的嘌呤；Y是未指定的嘧啶；在这里，我们报道了与免疫球蛋白轻链基因内含子增强子kappa B DNA结合的p50/p65异源二聚体在2.9埃分辨率下的晶体结构，我们的结构揭示了p50的5‘亚基对和p65的4 ’亚基对，这个结构说明了为什么p50/p65异源二聚体的界面比任何一种同型二聚体都强。这种结构与其他Rel二聚体的比较表明，这两个亚基都以dna序列依赖的方式采用可变构象。我们的结果解释了p50/p65异源二聚体与异源启动子的不同行为。
The NF-kappa B p50/p65 heterodimer is the classical member of the Rel family of transcription factors which regulate diverse cellular functions such as immune response, cell growth, and development(1-3). Other mammalian Rel family members, including the proteins p52, proto-oncoprotein c-Rel, and RelB, all have amino-terminal Rel-homology regions (RHRs)(4-7). The RHR is responsible for the dimerization, DNA binding and cytosolic localization of these proteins by virtue of complex formation with inhibitor kappa B proteins(8), Signal-induced removal of kappa B inhibitors allows translocation of dimers to the cell nucleus and transcriptional regulation of kappa B DNA-containing genes(9), NF-kappa B specifically recognizes kappa B DNA elements(1,10,11) with a consensus sequence of 5'-GGGRNYYYCC-3' (R is an unspecified purine; Y is an unspecified pyrimidine; and N is any nucleotide), Here we report the crystal structure at 2.9 Angstrom resolution of the p50/p65 heterodimer bound to the kappa B DNA of the intronic enhancer of the immunoglobulin light-chain gene, Our structure reveals a 5-base-pair 5' subsite for p50, and a 4-base-pair 3' subsite for p65, This structure indicates why the p50/p65 heterodimer interface is stronger than that of either homodimer, A comparison of this structure with those of other Rel dimers reveals that both subunits adopt variable conformations in a DNA-sequence-dependent manner. Our results explain the different behaviour of the p50/p65 heterodimer with heterologous promoters.