3P9Y

Crystal structure of the Drosophila melanogaster Ssu72-pCTD complex

Summary for 3P9Y

• Entry DOI: 10.2210/pdb3p9y/pdb
• Descriptor: CG14216, pSer5 CTD peptide, IMIDAZOLE, ... (5 entities in total)
• Functional Keywords: phosphatase, cis proline, lmw ptp-like fold, rna polymerase ii ctd, hydrolase
• Biological source: Drosophila melanogaster (Fruit fly); More
• Total number of polymer chains: 8
• Total formula weight: 96134.55

Authors

Werner-Allen, J.W.,Zhou, P. (deposition date: 2010-10-18, release date: 2010-12-15, Last modification date: 2016-08-17)

Primary citation

Werner-Allen, J.W.,Lee, C.J.,Liu, P.,Nicely, N.I.,Wang, S.,Greenleaf, A.L.,Zhou, P.
cis-Proline-mediated Ser(P)5 Dephosphorylation by the RNA Polymerase II C-terminal Domain Phosphatase Ssu72.
J.Biol.Chem., 286:5717-5726, 2011

PubMed Abstract: RNA polymerase II coordinates co-transcriptional events by recruiting distinct sets of nuclear factors to specific stages of transcription via changes of phosphorylation patterns along its C-terminal domain (CTD). Although it has become increasingly clear that proline isomerization also helps regulate CTD-associated processes, the molecular basis of its role is unknown. Here, we report the structure of the Ser(P)(5) CTD phosphatase Ssu72 in complex with substrate, revealing a remarkable CTD conformation with the Ser(P)(5)-Pro(6) motif in the cis configuration. We show that the cis-Ser(P)(5)-Pro(6) isomer is the minor population in solution and that Ess1-catalyzed cis-trans-proline isomerization facilitates rapid dephosphorylation by Ssu72, providing an explanation for recently discovered in vivo connections between these enzymes and a revised model for CTD-mediated small nuclear RNA termination. This work presents the first structural evidence of a cis-proline-specific enzyme and an unexpected mechanism of isomer-based regulation of phosphorylation, with broad implications for CTD biology.

PubMed: 21159777
DOI: 10.1074/jbc.M110.197129

Experimental method

X-RAY DIFFRACTION (2.1 Å)