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cis-Proline-mediated Ser(P)5 dephosphorylation by the RNA polymerase II C-terminal domain phosphatase Ssu72.

Publication ,  Journal Article
Werner-Allen, JW; Lee, C-J; Liu, P; Nicely, NI; Wang, S; Greenleaf, AL; Zhou, P
Published in: J Biol Chem
February 18, 2011

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.

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Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

February 18, 2011

Volume

286

Issue

7

Start / End Page

5717 / 5726

Location

United States

Related Subject Headings

  • Structure-Activity Relationship
  • RNA Polymerase II
  • Protein Structure, Tertiary
  • Proline
  • Phosphoprotein Phosphatases
  • Drosophila melanogaster
  • Drosophila Proteins
  • Crystallography, X-Ray
  • Biochemistry & Molecular Biology
  • Animals
 

Citation

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Werner-Allen, J. W., Lee, C.-J., Liu, P., Nicely, N. I., Wang, S., Greenleaf, A. L., & Zhou, P. (2011). cis-Proline-mediated Ser(P)5 dephosphorylation by the RNA polymerase II C-terminal domain phosphatase Ssu72. J Biol Chem, 286(7), 5717–5726. https://doi.org/10.1074/jbc.M110.197129
Werner-Allen, Jon W., Chul-Jin Lee, Pengda Liu, Nathan I. Nicely, Su Wang, Arno L. Greenleaf, and Pei Zhou. “cis-Proline-mediated Ser(P)5 dephosphorylation by the RNA polymerase II C-terminal domain phosphatase Ssu72.J Biol Chem 286, no. 7 (February 18, 2011): 5717–26. https://doi.org/10.1074/jbc.M110.197129.
Werner-Allen JW, Lee C-J, Liu P, Nicely NI, Wang S, Greenleaf AL, et al. cis-Proline-mediated Ser(P)5 dephosphorylation by the RNA polymerase II C-terminal domain phosphatase Ssu72. J Biol Chem. 2011 Feb 18;286(7):5717–26.
Werner-Allen, Jon W., et al. “cis-Proline-mediated Ser(P)5 dephosphorylation by the RNA polymerase II C-terminal domain phosphatase Ssu72.J Biol Chem, vol. 286, no. 7, Feb. 2011, pp. 5717–26. Pubmed, doi:10.1074/jbc.M110.197129.
Werner-Allen JW, Lee C-J, Liu P, Nicely NI, Wang S, Greenleaf AL, Zhou P. cis-Proline-mediated Ser(P)5 dephosphorylation by the RNA polymerase II C-terminal domain phosphatase Ssu72. J Biol Chem. 2011 Feb 18;286(7):5717–5726.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

February 18, 2011

Volume

286

Issue

7

Start / End Page

5717 / 5726

Location

United States

Related Subject Headings

  • Structure-Activity Relationship
  • RNA Polymerase II
  • Protein Structure, Tertiary
  • Proline
  • Phosphoprotein Phosphatases
  • Drosophila melanogaster
  • Drosophila Proteins
  • Crystallography, X-Ray
  • Biochemistry & Molecular Biology
  • Animals