Minezaki Yoshiaki, Homma Keiichi, Kinjo Akira R, Nishikawa Ken
Laboratory of Gene-Product Informatics, Center For Information Biology & DNA Data Bank of Japan, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan.
J Mol Biol. 2006 Jun 16;359(4):1137-49. doi: 10.1016/j.jmb.2006.04.016. Epub 2006 Apr 25.
Human transcriptional regulation factors, such as activators, repressors, and enhancer-binding factors are quite different from their prokaryotic counterparts in two respects: the average sequence in human is more than twice as long as that in prokaryotes, while the fraction of sequence aligned to domains of known structure is 31% in human transcription factors (TFs), less than half of that in bacterial TFs (72%). Intrinsically disordered (ID) regions were identified by a disorder-prediction program, and were found to be in good agreement with available experimental data. Analysis of 401 human TFs with experimental evidence from the Swiss-Prot database showed that as high as 49% of the entire sequence of human TFs is occupied by ID regions. More than half of the human TFs consist of a small DNA binding domain (DBD) and long ID regions frequently sandwiching unassigned regions. The remaining TFs have structural domains in addition to DBDs and ID regions. Experimental studies, particularly those with NMR, revealed that the transactivation domains in unbound TFs are usually unstructured, but become structured upon binding to their partners. The sequences of human and mouse TF orthologues are 90.5% identical despite a high incidence of ID regions, probably reflecting important functional roles played by ID regions. In general ID regions occupy a high fraction in TFs of eukaryotes, but not in prokaryotes. Implications of this dichotomy are discussed in connection with their functional roles in transcriptional regulation and evolution.
人类转录调控因子，如激活因子、抑制因子和增强子结合因子，在两个方面与原核生物的对应因子有很大不同：人类的平均序列长度是原核生物的两倍多，而人类转录因子（TFs）中与已知结构域对齐的序列比例为31%，不到细菌TFs（72%）的一半。通过无序预测程序鉴定出内在无序（ID）区域，发现其与现有实验数据高度一致。对来自瑞士蛋白质数据库的401个人类TFs进行实验证据分析表明，人类TFs整个序列中高达49%被ID区域占据。超过一半的人类TFs由一个小的DNA结合结构域（DBD）和经常夹着未分配区域的长ID区域组成。其余的TFs除了DBD和ID区域外还有结构域。实验研究，特别是那些利用核磁共振的研究，表明未结合的TFs中的反式激活结构域通常是无结构的，但在与它们的伙伴结合后会变得有结构。尽管ID区域的发生率很高，但人类和小鼠TF直系同源物的序列有90.5%是相同的，这可能反映了ID区域所起的重要功能作用。一般来说，ID区域在真核生物的TFs中占很高比例，但在原核生物中则不然。本文结合它们在转录调控和进化中的功能作用讨论了这种二分法的意义。
