An unexpected binding mode for a Pol II CTD peptide phosphorylated at Ser7 in the active site of the CTD phosphatase Ssu72.
Ssu72, an RNA polymerase II C-terminal domain (CTD) phospho-Ser5 (pSer5) phosphatase, was recently reported to have pSer7 phosphatase activity as well. We report here the crystal structure of a ternary complex of the N-terminal domain of human symplekin, human Ssu72, and a 10-mer pSer7 CTD peptide. Surprisingly, the peptide is bound in the Ssu72 active site with its backbone running in the opposite direction compared with a pSer5 peptide. The pSer7 phosphatase activity of Ssu72 is ∼4000-fold lower than its pSer5 phosphatase activity toward a peptide substrate, consistent with the structural observations.
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
Kehui
K
Xiang
James L
JL
Manley
Liang
L
Tong
D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D020134:Catalytic Domain; D004257:DNA Polymerase II / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D010455:Peptides / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary
D002352:Carrier Proteins; D010455:Peptides; D004257:DNA Polymerase II; D010749:Phosphoprotein Phosphatases; C496300:SSU72 protein, human; C116022:carboxy-terminal domain phosphatase; D010744:Phosphoric Monoester Hydrolases