COGNATE DNA-BINDING SPECIFICITY RETAINED AFTER LEUCINE ZIPPER EXCHANGE BETWEEN GCN4 AND C/EBP

COGNATE DNA-BINDING SPECIFICITY RETAINED AFTER LEUCINE ZIPPER EXCHANGE BETWEEN GCN4 AND C/EBP
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DOI:
10.1126/science.2530632
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发表时间:
1989-11-17
期刊:
影响因子:
56.9
通讯作者:
MCKNIGHT, SL
MCKNIGHT, SL
中科院分区:
综合性期刊1区
文献类型:
--
作者:
AGRE, P;JOHNSON, PF;MCKNIGHT, SL

文献摘要

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C/EBP和GCN 4都是控制基因表达的序列特异性DNA结合蛋白。最近的证据表明C/EBP作为参与脂质和碳水化合物代谢的基因的转录调节因子。C/EBP蛋白与二分体对称序列5“-ATTGCGCAAT-3”紧密结合; GCN 4调节酵母中控制氨基酸生物合成的基因的转录,并与二分体对称序列5“-ATGA(G/C)TCAT-3”紧密结合。C/EBP和GCN 4都通过相同的结构基序结合DNA。该基序被预测为二分的,由称为“亮氨酸拉链”的二聚化界面和称为“碱性区域”的DNA接触表面组成。“DNA结合的特异性被预测是由碱性区域赋予的。作为该假设的测试,产生了重组蛋白,其中GCN 4和C/EBP的碱性区和亮氨酸拉链是互补交换的。在这两种重组多肽中,DNA结合特异性显示为与碱性区域一起追踪。
Both C/EBP and GCN4 are sequence-specific DNA binding proteins that control gene expression. Recent evidence implicates C/EBP as a transcriptional regulator of genes involved in lipid and carbohydrate metabolism. The C/EBP protein binds avidly to the dyad symmetric sequence 5''-ATTGCGCAAT-3''; GCN4 regulates the transcription of genes that control amino acid biosynthesis in yeast, and binds avidly to the dyad symmetric sequence 5''-ATGA(G/C)TCAT-3''. Both C/EBP and GCN4 bind DNA via the same structural motif. This motif has been predicted to be bipartite, consisting of a dimerization interface termed the "leucine zipper" and a DNA contact surface termed the "basic region." Specificity of DNA binding has been predicted to be imparted by the basic region. As a test of this hypothesis, recombinant proteins were created wherein the basic regions and leucine zippers of GCN4 and C/EBP were reciprocally exchanged. In both of the recombinant polypeptides, DNA binding specificity is shown to track with the basic region.