PAS IS A DIMERIZATION DOMAIN COMMON TO DROSOPHILA PERIOD AND SEVERAL TRANSCRIPTION FACTORS
PAS IS A DIMERIZATION DOMAIN COMMON TO DROSOPHILA PERIOD AND SEVERAL TRANSCRIPTION FACTORS
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DOI：
10.1038/364259a0
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发表时间：
1993-07-15
期刊：
影响因子：
64.8
通讯作者：
ROSBASH, M
中科院分区：
文献类型：
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作者：
HUANG, ZJ;EDERY, I;ROSBASH, M
周期基因产物（PER）的突变可以缩短或延长果蝇的昼夜节律，但其生化活性尚未确定。PER含有一个约270个氨基酸的基序，其功能尚不清楚（称为PAS 2），也存在于三种基本螺旋环螺旋（bHLH）型转录因子中，在D.黑腹动物的单头脑基因产物（SIM）2，并在两个亚基的哺乳动物二恶英受体复合物3，4，28。我们在这里表明，PER PAS功能在体外作为一种新的蛋白质二聚化基序，它可以介导的PAS蛋白质家族的不同成员之间的关联。PAS结构域中的几个错义突变降低了二聚化效率，包括原始的per（L）突变，其将昼夜节律周期从24小时延长至29小时（参考文献1）。结果表明，PAS结构域在SIM和二恶英受体复合物中均具有二聚化结构域的功能，PER可能部分通过与bHLH-PAS转录因子的PAS结构域相互作用来调节昼夜节律基因的转录。
MUTATIONS in the period gene product (PER) can shorten or lengthen the circadian rhythms of Drosophila melanogaster1, but its biochemical activity has not been established. PER contains a motif of approximately 270 amino acids whose function is unknown (termed PAS2) and which is also present in three transcription factors of the basic-helix-loop-helix (bHLH) type, in the D. melanogaster single-minded gene product (SIM)2, and in both subunits of the mammalian dioxin receptor complex3,4,28. We show here that the PER PAS functions in vitro as a novel protein dimerization motif and that it can mediate associations between different members of the PAS protein family. The dimerization efficiency is decreased by several missense mutations in the PAS domain, including the original per(L) mutation, which lengthens circadian periods from 24 h to 29 h (ref. 1). The results indicate that the PAS domain may function as a dimerization domain in both SIM and the dioxin receptor complex, and that PER may regulate circadian gene transcription partly by interacting with the PAS domain of bHLH-PAS-containing transcription factors.