cis-Proline-mediated Ser(P)5 dephosphorylation by the RNA polymerase II C-terminal domain phosphatase Ssu72.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Werner-Allen, JW; Lee, C-J; Liu, P; Nicely, NI; Wang, S; Greenleaf, AL; Zhou, P
Published Date
- February 18, 2011
Published In
Volume / Issue
- 286 / 7
Start / End Page
- 5717 - 5726
PubMed ID
- 21159777
Pubmed Central ID
- PMC3037684
Electronic International Standard Serial Number (EISSN)
- 1083-351X
Digital Object Identifier (DOI)
- 10.1074/jbc.M110.197129
Language
- eng
Conference Location
- United States