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PMID:21159777

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Citation

Werner-Allen, JW, Lee, CJ, Liu, P, Nicely, NI, Wang, S, Greenleaf, AL and Zhou, P (2011) cis-Proline-mediated Ser(P)5 dephosphorylation by the RNA polymerase II C-terminal domain phosphatase Ssu72. J. Biol. Chem. 286:5717-26

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.

Links

PubMed PMC3037684 Online version:10.1074/jbc.M110.197129

Keywords

Animals; Crystallography, X-Ray; Drosophila Proteins/chemistry; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster; Phosphoprotein Phosphatases/chemistry; Phosphoprotein Phosphatases/genetics; Phosphoprotein Phosphatases/metabolism; Proline; Protein Structure, Tertiary; RNA Polymerase II/chemistry; RNA Polymerase II/genetics; RNA Polymerase II/metabolism; Structure-Activity Relationship

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:M9PHZ3

involved_in

GO:0006470: protein dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:M9PHZ3

enables

GO:0008420: RNA polymerase II CTD heptapeptide repeat phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:M9PHZ3

involved_in

GO:0070940: dephosphorylation of RNA polymerase II C-terminal domain

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VWE4

involved_in

GO:0006470: protein dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VWE4

enables

GO:0008420: RNA polymerase II CTD heptapeptide repeat phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:Q9VWE4

involved_in

GO:0070940: dephosphorylation of RNA polymerase II C-terminal domain

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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