The Structure of Fcp1, an Essential RNA Polymerase II CTD Phosphatase

Agnidipta Ghosh, Stewart Shuman, Christopher D. Lima

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Kinases and phosphatases regulate mRNA synthesis and processing by phosphorylating and dephosphorylating the C-terminal domain (CTD) of the largest subunit of RNA polymerase II. Fcp1 is an essential CTD phosphatase that preferentially hydrolyzes Ser2-PO4 of the tandem YSPTSPS CTD heptad array. Fcp1 crystal structures were captured at two stages of the reaction pathway: a Mg-BeF3 complex that mimics the aspartylphosphate intermediate and a Mg-AlF4 - complex that mimics the transition state of the hydrolysis step. Fcp1 is a Y-shaped protein composed of an acylphosphatase domain located at the base of a deep canyon formed by flanking modules that are missing from the small CTD phosphatase (SCP) clade: an Fcp1-specific helical domain and a C-terminal BRCA1 C-terminal (BRCT) domain. The structure and mutational analysis reveals that Fcp1 and Scp1 (a Ser5-selective phosphatase) adopt different CTD-binding modes; we surmise the CTD threads through the Fcp1 canyon to access the active site.

Original languageEnglish (US)
Pages (from-to)478-490
Number of pages13
JournalMolecular Cell
Volume32
Issue number4
DOIs
StatePublished - Nov 21 2008
Externally publishedYes

Fingerprint

RNA Polymerase III
RNA Polymerase II
Phosphoric Monoester Hydrolases
Catalytic Domain
Hydrolysis
Phosphotransferases
Messenger RNA
Proteins

Keywords

  • PROTEINS
  • RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

The Structure of Fcp1, an Essential RNA Polymerase II CTD Phosphatase. / Ghosh, Agnidipta; Shuman, Stewart; Lima, Christopher D.

In: Molecular Cell, Vol. 32, No. 4, 21.11.2008, p. 478-490.

Research output: Contribution to journalArticle

Ghosh, Agnidipta ; Shuman, Stewart ; Lima, Christopher D. / The Structure of Fcp1, an Essential RNA Polymerase II CTD Phosphatase. In: Molecular Cell. 2008 ; Vol. 32, No. 4. pp. 478-490.
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