MUTAGENESIS OF THE MYOGENIN BASIC REGION IDENTIFIES AN ANCIENT PROTEIN MOTIF CRITICAL FOR ACTIVATION OF MYOGENESIS
MUTAGENESIS OF THE MYOGENIN BASIC REGION IDENTIFIES AN ANCIENT PROTEIN MOTIF CRITICAL FOR ACTIVATION OF MYOGENESIS
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DOI：
10.1073/pnas.88.13.5675
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发表时间：
1991-07-01
影响因子：
11.1
通讯作者：
OLSON, EN
中科院分区：
文献类型：
--
作者：
BRENNAN, TJ;CHAKRABORTY, T;OLSON, EN
肌细胞生成素是一种肌肉特异性核因子，作为基因开关激活肌细胞生成。肌细胞生成素、MyoD和越来越多的参与转录控制的蛋白质在碱性区域和相邻的螺旋-环-螺旋基序内共享序列同源性。在这里，我们通过定点诱变确定了一个12个氨基酸的肌细胞生成素的基本区域的亚结构域的DNA结合和激活肌细胞生成所必需的。广泛表达的螺旋-环-螺旋蛋白E12的碱性区域在这12个残基中的8个残基处是保守的，并且当置于肌细胞生成素中时可以介导DNA结合，但它不能激活肌细胞生成。用E12的相应残基替换肌细胞生成素碱性区的四个非保守残基中的每一个，揭示了两个相邻的氨基酸（Ala 86-Thr 87），其可以赋予碱性区肌肉特异性。这些残基是特定的，并保守的，从果蝇到人的所有已知的生肌螺旋-环-螺旋蛋白的基本区域，这表明它们构成了一个古老的蛋白质基序激活的生肌程序所需的一部分。
Myogenin is a muscle-specific nuclear factor that acts as a genetic switch to activate myogenesis. Myogenin, MyoD, and a growing number of proteins implicated in transcriptional control share sequence homology within a basic region and an adjacent helix-loop-helix motif. Here we identify by site-directed mutagenesis a 12-amino acid subdomain of the myogenin basic region essential for binding of DNA and activation of myogenesis. The basic region of the widely expressed helix-loop-helix protein E12 is conserved at 8 of these 12 residues and can mediate DNA binding when placed in myogenin, but it cannot activate myogenesis. Replacement of each of the four nonconserved residues of the myogenin basic region with the corresponding residues of E12 reveals two adjacent amino acids (Ala86-Thr87) that can impart muscle specificity to the basic region. These residues are specific to, and conserved in, the basic regions of all known myogenic helix-loop-helix proteins from Drosophila to man, suggesting that they constitute part of an ancient protein motif required for activation of the myogenic program.