STRUCTURAL BASIS FOR DNA BENDING BY THE ARCHITECTURAL TRANSCRIPTION FACTOR LEF-1
STRUCTURAL BASIS FOR DNA BENDING BY THE ARCHITECTURAL TRANSCRIPTION FACTOR LEF-1
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DOI：
10.1038/376791a0
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发表时间：
1995-08-31
期刊：
影响因子：
64.8
通讯作者：
WRIGHT, PE
中科院分区：
文献类型：
--
作者：
LOVE, JJ;LI, XA;WRIGHT, PE
淋巴增强子结合因子 (LEF-1) 和密切相关的 T 细胞因子 1 (TCF-1) 是序列特异性和细胞类型特异性 DNA 结合蛋白，在器官发生和胸腺细胞分化中发挥重要的调节作用 (1-5)。 LEF-1 通过诱导 DNA 急剧弯曲并促进结合在 LEF-1 位点侧翼位点的 Ets-1、PEBP2-α 和 ATF/CREB 转录因子之间的相互作用来参与与 T 细胞受体 (TCR)-alpha 基因相关的增强子的调节 (1,2,6,7)。 LEF-1 似乎在该调节性核蛋白复合物的组装和功能中发挥着结构性作用(7,8)。 LEF-1 通过高迁移率基团 (HMG) 结构域识别特定的核苷酸序列(1,2)。含有 HMG 结构域的蛋白质在小沟中结合 DNA，弯曲双螺旋 (6,9,10)，并识别四路连接和其他不规则 DNA 结构 (9,11)。在这里，我们报告了 LEF-1 HMG 结构域和相邻碱性区域及其同源 DNA 的复合物的溶液结构。该结构揭示了 HMG 结构域结合在明显扭曲和弯曲的双螺旋的加宽小沟中。碱性区域与狭窄的主沟结合并有助于 DNA 识别。
LYMPHOID enhancer-binding factor (LEF-1) and the closely related T-cell factor 1 (TCF-1) are sequence-specific and cell-type-specific DNA-binding proteins that play important regulatory roles in organogenesis and thymocyte differentiation(1-5). LEF-1 participates in regulation of the enhancer associated with the T cell receptor (TCR)-alpha gene by inducing a sharp bend in the DNA and facilitating interactions between Ets-1, PEBP2-alpha, and ATF/CREB transcription factors bound at sites flanking the LEF-1 site(1,2,6,7). It seems that LEF-1 plays an architectural role in the assembly and function of this regulatory nucleoprotein complex(7,8). LEF-1 recognizes a specific nucleotide sequence through a high-mobilty-group (HMG) domain(1,2). Proteins containing HMG domains bind DNA in the minor groove, bend the double helix(6,9,10), and recognize four-way junctions and other irregular DNA structures(9,11). Here we report the solution structure of a complex of the LEF-1 HMG domain and adjacent basic region with its cognate DNA. The structure reveals the HMG domain bound in the widened minor groove of a markedly distorted and bent double helix. The basic region binds across the narrowed major groove and contributes to DNA recognition.