cis-Proline-mediated Ser(P)[superscript 5] Dephosphorylation by the RNA Polymerase II C-terminal Domain Phosphatase Ssu72

Journal Article · Wed May 16 04:00:00 EDT 2012 · Journal of Biological Chemistry

DOI:https://doi.org/10.1074/jbc.M110.197129· OSTI ID:1040638

Werner-Allen, Jon W; Lee, Chul-Jin; Liu, Pengda; Nicely, Nathan I; Wang, Su; Greenleaf, Arno L; Zhou, Pei ^[1]

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1. Duke

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){sup 5} CTD phosphatase Ssu72 in complex with substrate, revealing a remarkable CTD conformation with the Ser(P){sup 5}-Pro{sup 6} motif in the cis configuration. We show that the cis-Ser(P){sup 5}-Pro{sup 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

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: OTHERNIH
• OSTI ID: 1040638
• Journal Information: Journal of Biological Chemistry, Journal Name: Journal of Biological Chemistry Journal Issue: 7 Vol. 286; ISSN 0021-9258; ISSN JBCHA3
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
BIOLOGY
CONFIGURATION
ENZYMES
IN VIVO
ISOMERIZATION
ISOMERS
PHOSPHATASES
PHOSPHORYLATION
PROLINE
RNA
RNA POLYMERASES
TRANSCRIPTION