作　者：Liu J, Zhang J, Gong Q, Xiong P, Huang H, Wu B, Lu G, Wu J, Shi Y.

Abstract：Spt6 is an evolutionally-conserved eukaryotic transcriptional elongation factor, which directly binds the RNA polymerase II C-terminal domain (RNAPII CTD) through a SH2 domain that can recognize phosphoserine. In this study, we discovered a novel SH2 domain just downstream the phosphoserine binding SH2 domain in Spt6, and determined the solution structure of this rigidly-linked tandem SH2 domain module of Spt6 from Saccharomyces cerevisiae. Structure and evolution analysis reveal that this novel SH2 domain is evolutionally distant from canonical SH2 domains, and suggest it represents a novel SH2 subfamily, whose function and interaction partner are still mysterious. NMR titration experiments show that the first SH2 domain recognizes both the phosphoserine and phosphotyrosine residue of RNAPII CTD with milimolar affinity; while the second SH2 domain lacks the CTD binding ability. The tandem SH2 domain’s binding affinities to different phosphorylation pattern of CTD agree well with its function in transcription.