Hirai S, Yaniv M
UA 1149 du CNRS, Département de Biologie Moléculaire, Institut Pasteur, Paris, France.
New Biol. 1989 Nov;1(2):181-91.
Mutations between the leucines of the "leucine zipper" domain of Jun D can either decrease (Asn 301 to Ala) or increase (Thr 307, Ala 308, to Glu, Val) homodimer formation and specific binding to DNA even though such changes do not modify the predicted alpha-helical structure of this region. As shown previously, addition of Fos strongly increases the affinity of Jun for DNA by forming a heterodimer. The jun down mutation (Asn 301 to Ala) also diminishes DNA binding by the Fos-Jun D heterodimer. These data strongly support the coiled coil conformation of this region where residues adjacent to the leucines are also important for dimer formation. Ultraviolet cross-linking experiments have shown that both Fos and Jun directly contact the TGACTCA palindromic sequence defined as a TPA (12-O-tetradecanoyl phorbol-13-acetate) response element or TRE. Both Jun homodimers and Jun-Fos heterodimers bind this TRE as well as the cAMP responsive element (CRE or TGACGTCA) with comparable affinities. While strong c-Jun or Jun D binding requires a perfect palindrome, Jun-Fos complexes can also efficiently recognize sequences where the right half of the palindrome is less conserved (TGACTAA or TGACGCA).
Jun D的“亮氨酸拉链”结构域中亮氨酸之间的突变，既可以降低（天冬酰胺301突变为丙氨酸）也可以增加（苏氨酸307、丙氨酸308突变为谷氨酸、缬氨酸）同二聚体的形成以及与DNA的特异性结合，尽管这些变化不会改变该区域预测的α螺旋结构。如前所示，添加Fos通过形成异二聚体可强烈增加Jun与DNA的亲和力。Jun的下调突变（天冬酰胺301突变为丙氨酸）也会减少Fos-Jun D异二聚体与DNA的结合。这些数据有力地支持了该区域的卷曲螺旋构象，其中与亮氨酸相邻的残基对二聚体形成也很重要。紫外线交联实验表明，Fos和Jun都直接接触被定义为佛波酯（12-O-十四烷酰佛波醇-13-乙酸酯）反应元件或TRE的TGACTCA回文序列。Jun同二聚体和Jun-Fos异二聚体以相当的亲和力结合该TRE以及cAMP反应元件（CRE或TGACGTCA）。虽然强c-Jun或Jun D结合需要完美的回文序列，但Jun-Fos复合物也能有效识别回文序列右半部分保守性较低的序列（TGACTAA或TGACGCA）。
