Gene Center Munich and Department of Biochemistry, Center for Integrated Protein Science Munich, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.
J Biol Chem. 2010 Dec 31;285(53):41597-603. doi: 10.1074/jbc.M110.144568. Epub 2010 Oct 6.
Spt6 is an essential transcription elongation factor and histone chaperone that binds the C-terminal repeat domain (CTD) of RNA polymerase II. We show here that Spt6 contains a tandem SH2 domain with a novel structure and CTD-binding mode. The tandem SH2 domain binds to a serine 2-phosphorylated CTD peptide in vitro, whereas its N-terminal SH2 subdomain, which we previously characterized, does not. CTD binding requires a positively charged crevice in the C-terminal SH2 subdomain, which lacks the canonical phospho-binding pocket of SH2 domains and had previously escaped detection. The tandem SH2 domain is apparently required for transcription elongation in vivo as its deletion in cells is lethal in the presence of 6-azauracil.
Spt6 是一种必需的转录延伸因子和组蛋白伴侣，可与 RNA 聚合酶 II 的 C 端重复结构域 (CTD) 结合。我们在这里表明，Spt6 包含一个串联 SH2 结构域，具有新颖的结构和 CTD 结合模式。串联 SH2 结构域在体外与丝氨酸 2 位磷酸化的 CTD 肽结合，而我们之前表征的 N 端 SH2 亚结构域则不结合。CTD 结合需要 C 端 SH2 亚结构域中带正电荷的裂隙，该裂隙缺乏 SH2 结构域的典型磷酸结合口袋，以前未被发现。串联 SH2 结构域显然是体内转录延伸所必需的，因为在 6-氮杂尿嘧啶存在的情况下，其在细胞中的缺失是致命的。
