O'Shea E K, Rutkowski R, Kim P S
Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
Cell. 1992 Feb 21;68(4):699-708. doi: 10.1016/0092-8674(92)90145-3.
Fos and Jun, the protein products of the nuclear proto-oncogenes c-fos and c-jun, associate preferentially to form a heterodimer that binds to DNA and modulates transcription of a wide variety of genes in response to mitogenic stimuli. Both Fos and Jun contain a single leucine zipper region. Previous studies have shown that the leucine zippers of Fos and Jun are necessary and sufficient to mediate preferential heterodimer formation. The leucine zipper regions from Fos and Jun are also known to fold autonomously, most likely as two-stranded, parallel coiled coils. We show here that 8 amino acids from Fos and from Jun are sufficient to mediate preferential heterodimer formation in a background of the GCN4 leucine zipper sequence. Using pH titration and amino acid replacements, we also show that destabilization of the Fos homodimer by acidic residues provides a major thermodynamic driving force for preferential heterodimer formation.
原癌基因c-fos和c-jun的蛋白质产物Fos和Jun优先结合形成异二聚体，该异二聚体可结合DNA并响应有丝分裂刺激调节多种基因的转录。Fos和Jun都含有一个亮氨酸拉链区域。先前的研究表明，Fos和Jun的亮氨酸拉链对于介导优先的异二聚体形成是必要且充分的。Fos和Jun的亮氨酸拉链区域也已知能自主折叠，很可能形成双链平行卷曲螺旋。我们在此表明，来自Fos和Jun的8个氨基酸足以在GCN4亮氨酸拉链序列的背景下介导优先的异二聚体形成。通过pH滴定和氨基酸替换，我们还表明酸性残基使Fos同二聚体不稳定，这为优先的异二聚体形成提供了主要的热力学驱动力。
