Macdonald Neil, Welburn Julie P I, Noble Martin E M, Nguyen Anhco, Yaffe Michael B, Clynes David, Moggs Jonathan G, Orphanides George, Thomson Stuart, Edmunds John W, Clayton Alison L, Endicott Jane A, Mahadevan Louis C
Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, SK10 4TJ, United Kingdom.
Mol Cell. 2005 Oct 28;20(2):199-211. doi: 10.1016/j.molcel.2005.08.032.
Phosphorylation of histone H3 is implicated in transcriptional activation and chromosome condensation, but its immediate molecular function has remained obscure. By affinity chromatography of nuclear extracts against modified H3 tail peptides, we identified 14-3-3 isoforms as proteins that bind these tails in a strictly phosphorylation-dependent manner. Acetylation of lysines 9 and 14 does not impede 14-3-3 binding to serine 10-phosphorylated H3 tails. In vivo, 14-3-3 is inducibly recruited to c-fos and c-jun nucleosomes upon gene activation, concomitant with H3 phosphoacetylation. We have determined the structures of 14-3-3zeta complexed with serine 10-phosphorylated or phosphoacetylated H3 peptides. These reveal a distinct mode of 14-3-3/phosphopeptide binding and provide a structural understanding for the lack of effect of acetylation at lysines 9 and 14 on this interaction. 14-3-3 isoforms thus represent a class of proteins that mediate the effect of histone phosphorylation at inducible genes.
组蛋白H3的磷酸化与转录激活和染色体凝聚有关，但其直接的分子功能仍不清楚。通过针对修饰的H3尾肽对核提取物进行亲和层析，我们鉴定出14-3-3亚型是一类以严格的磷酸化依赖性方式结合这些尾肽的蛋白质。赖氨酸9和14的乙酰化并不妨碍14-3-3与丝氨酸10磷酸化的H3尾肽结合。在体内，基因激活时，14-3-3可被诱导募集到c-fos和c-jun核小体上，同时伴有H3磷酸乙酰化。我们已经确定了与丝氨酸10磷酸化或磷酸乙酰化的H3肽复合的14-3-3ζ的结构。这些结构揭示了14-3-3/磷酸肽结合的独特模式，并为赖氨酸9和14的乙酰化对这种相互作用缺乏影响提供了结构上的理解。因此，14-3-3亚型代表了一类介导诱导型基因上组蛋白磷酸化作用的蛋白质。
